NICHD–INSERM Scholar Program
APPLICATION INSTRUCTIONS
Application Deadline:
Notification of Award:
Begin Fellowship by:
February 15, 2016
April 30, 2016
September 1, 2016
The NICHD–Inserm Scholar program provides a unique opportunity for U.S. and French scientists to
obtain postdoctoral training with French and U.S. mentors, respectively. The binational postdoctoral
research fellowships are cosponsored by the National Institute on Child and Human Development
(NICHD) and Institut National de la Santé et de la Recherche Médicale (Inserm).
Each fellow benefits from an intensive research training experience designed to enhance the
fellow’s ability to conduct independent research upon return to his or her home country.
In fiscal year 2016, NICHD will support one award for French scientists to work in the United States
with a mentor at NICHD-DIR (Division of Intramural Research), and Inserm will support one award
for U.S. scientists to work in France with a mentor at an Inserm research unit or center.
NICHD–Inserm Fellowships are awarded for a 12-month continuous period of time with an option to
renew the fellowship once (after evaluation of the first fellowship period). Successful candidates will
be required to agree to complete the full 12-month fellowship period.
WHAT THE FELLOWSHIPS PROVIDE
French scientists spending their fellowship in the United States will receive from NICHD an annual
stipend of approximately $46,000USD for living and personal expenses and an estimated $8,000USD
supplemental funding to cover the cost of personal health insurance (single coverage rate) that must meet
the health insurance requirements specified in the J-1 regulations, and professional development
activities. NICHD will provide one round-trip, economy class airfare for the fellow only.
U.S. scientists spending their fellowship in France will be employed by Inserm under a temporary
contract providing an annual gross salary of 34 200€ – 45 600€ depending upon the number of years
of postdoctoral experience, including personal health insurance. Inserm will provide one round-trip,
economy class Washington, DC-France airfare for the fellow only.
Updated 04/2015
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NICHD–INSERM Scholar Program
REQUIREMENTS FOR APPLICANTS
French applicants must:
Hold an earned doctoral degree in medicine or biomedical sciences.
Have completed postdoctoral research in an Inserm unit (for more than 2 years but less
than 5 years total, with a PhD obtained within the past 5 years), demonstrating the
ability to engage in independent research.
Be a citizen or permanent resident of France.
Live and work in France, in an Inserm research unit, at the time the application is
submitted.
Be eligible for a J-1 visa to enter the United States.
Be proficient in written and spoken English.
U.S. applicants must:
Hold an earned doctoral degree in medicine or biomedical sciences.
Have completed postdoctoral research demonstrating the ability to engage in independent
research.
Be a citizen or permanent resident of the United States.
Live and work in the United States at the time the application is submitted.
Be eligible for a temporary-stay visa to work in France.

REQUIREMENTS FOR MENTORS
French mentors:
Must be conducting research in two main topics: Imaging/Quantitative Biology and Early
Development (this term to be interpreted as broadly as possible). These topics correspond to
priority in France.
Must be a researcher with one of the laboratories included in the “List of Inserm’s Host
Laboratories and Research Programs”sheet.
U.S. mentors:
Should be a current NICHD Principal Investigator conducting research in
Imaging/Quantitative Biology and Early Development whose project will be active
throughout the proposed fellowship period.
Must be a researcher included in the List of NICHD Mentors.
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NICHD–INSERM Scholar Program
APPLICATION OVERVIEW
The NICHD–Inserm Scholar program application requires careful and thorough coordination
between the applicant and mentor. Individuals wishing to apply must:
Contact an eligible researcher who is willing to serve as a mentor.
o U.S applicants refer to the “List of Inserm’s Host Laboratories and Research
Programs” to identify an eligible researcher.
o French applicants refer to the “List of Prospective NICHD Mentor”s to identify an
eligible researcher.
Notify the NICHD and the Inserm Department of National and Foreign Affairs of their
plans to apply.
Write no more than three -page Research Plan for working with the mentor to investigate
Imaging/Quantitative Biology and/or Early Development.
Have the mentor complete his or her section of the application and submit it to the
appropriate agency.
APPLICATION INSTRUCTIONS
1. Incomplete applications will NOT be reviewed.
2. Applications must be typewritten, single-spaced, and single-sided. Applications must be written
in English language only.
3. Applicant must complete Part I, Part III—Applicant Section, Part IV, Part V, and Part VI.
Applicant should ensure he/she has signed the Applicant Certification and Acceptance section
of Part I.
4. Applicant should attach all supporting documents listed on Part III–Application Checklist.
5. Applicant should forward his/her completed sections of the application to the eligible U.S. or
French scientist who has agreed to be his/her mentor.
6. The mentor will then complete Part II, Part III—Mentor Section, Part VII, Part VIII, Part IX,
and Part X. The mentor should ensure he/she has signed the Mentor Certification and
Acceptance section of Part II
French applicants: On Part X–Sponsoring Institution Certifications and Assurances,
signatures are required from the U.S. mentor, the department head, and an official
signing for the sponsoring institution. The sponsoring institution official must be a
separate individual from the mentor.
U.S. applicants: On Part X–Sponsoring Institution Certifications and Assurances,
signatures are required from the French mentor (the supervising scientist at the host
laboratory), the director of the host laboratory, and the Inserm Regional Delegate.
7. The mentor should attach all supporting documents listed on Part III–Application Checklist.
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NICHD–INSERM Scholar Program
8. Once all signatures are secured and supporting documents attached, the mentor should submit
the application.
French applicants: The U.S. mentor should submit the application to the NICHD.
U.S. applicants: The French mentor should submit the application to the International
affairs of the Inserm Department of National and Foreign Affairs (DPRE).
PROFESSIONAL REFERENCES
On the Reference Report, the applicant completes Part I of the form. The applicant should provide
a copy of the Reference Report form to each of two professional references.
Each reference will complete Part II of the Reference Report including the rating scale. Each
reference also must attach a letter of reference as explained in Part III. For French applicants, each
reference must submit the completed Reference Report and letter of reference directly to the
NICHD by email. For US applicants, each reference must submit the completed Reference Report
and letter of reference directly to the International affairs of the Inserm by email.
APPLICATION AND REFERENCE SUBMISSION
Submit the completed documents electronically by the February 15 deadline to:
NICHD
Inserm
Office of the Scientific
Inserm-USA Office
Director,
Embassy of France in the US
Rm. 2A46, 31 Center Dr.
4101 Reservoir Rd, NW
Bethesda, MD 20892-2425
Washington, DC 20007
USA
Telephone: +1 202 944 6253
Telephone: 301-451-7753
Contact: Mireille Guyader at
Contact: Brenda Hanning
Inserm-usa@ambascience-usa.org
at hanningb@mail.nih.gov
Each participant will evaluate their own candidates following their agreed internal procedure. The results of the
evaluation and the selection of the candidates will be then discussed between the parties in order to reach a
common approval.
FOR MORE INFORMATION
http://www.nichd.nih.gov and http://www.inserm.fr
Email: brenda.hanning@nichd.nih.gov OR mireille.guyader@ambascience-usa.org
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NICHD–INSERM Scholar Program
PREPARING YOUR NICHD–INSERM FELLOWSHIP RESEARCH PLAN
The Research Plan (Part VI) is the most important part of the application. This section should be
well formulated and presented in sufficient detail so that reviewers can evaluate its scientific merit.
The applicant should actively seek the advice and cooperation of the mentor while preparing the
Research Plan. The mentor’s collaboration is important, but the applicant must write the Research
Plan. Be specific and informative, and avoid redundancy. Brevity and clarity in the description of
the Research Plan are considered indicative of an applicant’s approach to the research objective
and ability to conduct a superior project. The Research Plan should not exceed three pages in
addition to the face page. Literature citations are not included in the page limit. The applicant
should use the following format:
1. Specific Aims. State the specific purposes of the research and the hypotheses to be tested.
2. Background and Significance. Briefly describe the background of the Research Plan. This is
an important consideration in the initial review of your application. Concisely state the
importance of the Research Plan by relating specific aims to broad, long-term objectives.
3. Research Design and Methods. Discuss in detail the following:
a. The research design and procedures to be used to accomplish the specific aims
b. Sampling design, if conducting primary data collection
c. The analytic plan detailing the statistical approach to addressing the hypotheses
d. Any precautions necessary for procedures, situations, or materials that may be hazardous
to personnel
e. Potential limitations of the proposed project
f. The timeline for completion of the proposed investigation
g. The contributions that this project will make to the field of Imaging/Quantitative Biology
and/or Early Development.
4.
NIH Regulations on the Conduct of Research. Research conducted in the United States as
part of a NICHD–Inserm Fellowship is subject to the same U.S. Federal regulations, policies,
guidelines, and review considerations as are all National Institutes of Health (NIH) research
project grant applications. In this section of the Research Plan, applicants must demonstrate
that they understand and have planned to comply with those rules, particularly if the research
involves human subjects or vertebrate animals. For a complete discussion of the NIH
regulations,
consult
the
NIH
Grants
Policy
Statement
at
http://grants.nih.gov/grants/policy/nihgps_2010/index.htm or Part III, Section 2 of the U.S.
Department of Health and Human Services, Public Health Service Grant Application, PHS
398 Instructions, http://grants2.nih.gov/grants/funding/phs398/phs398.html.
5. Inserm Regulations on the Conduct of Research. Research conducted in France as part of a
NICHD–Inserm Fellowship is subject to the same French and European regulations, policies,
guidelines and review considerations as are all research projects and activities performed
within and/or supported by Inserm. In this section of the Research Plan, applicants must
demonstrate that they understand and have planned to comply with those rules, particularly if
the research involves human subjects or vertebrate animals. For a complete discussion of the
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NICHD–INSERM Scholar Program
Inserm regulations, please contact secretariat.daj@inserm.fr
6. Literature Citations. Provide literature citations at the end of the Research Plan. Each citation
must include the authors’ names, book or journal titles, volume number, page numbers, and
year of publication.
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NICHD–INSERM Scholar Program
REVIEW CRITERIA
Applications are peer-reviewed through a competitive process and assessed according to scientific
merit, the proposal’s relevance to cell biology and NICHD’s and Inserm’s research missions,
adequacy of the applicant’s education and experience to conduct the proposed research, likelihood
that the proposed research can be completed within the proposed timeline, and compatibility of the
applicant’s and mentor’s objectives. Several factors may enhance the rating of an application, even
though all of these items are not necessarily required.
APPLICANT
Previous experience and education are commensurate with the proposed study.
Although not yet considered a senior scientist, the applicant has demonstrated sufficient
research experience to successfully complete the proposed study.
The letters of reference support the applicant’s scientific record.
The applicant has authored a peer-reviewed scientific article in the area of the proposed
research.
RESEARCH PLAN
Describes how the proposed study is unique, how it will expand or advance the field of
drug abuse research, and how it is consistent with the applicant’s career goals.
Clearly and concisely states proposed aims, goals, and objectives appropriate to the stated
hypotheses, conveying scientific sophistication and strong analytical skills.
Thoroughly reviews the relevant literature.
Acknowledges any potential regulatory issues or methodological limitations.
Clearly states the applicant’s role in the proposed research and the collaborative plan
between the applicant and the mentor.
Describes what skills and experiences will be gained in the process of working with the
mentor,why that proposed training would not otherwise be available to the applicant, and
how those skills will be utilized when the applicant returns home.
Includes a realistic timeline for completing the proposed study within the fellowship
period.
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NICHD–INSERM Scholar Program
Application
U.S. Applicant
French Applicant
(English Language Only)
Part I—Applicant Information
1. Name of Applicant (family name, given name, middle initial):
2. Advanced Degree(s):
3. Position Title:
4. Name of Institution:
5. Department, Division, Service, Laboratory:
6. Institution Mailing Address (street address, city, state, postal code):
7. Country:
8. Office Phone (country code, city code, number):
9. Office Fax (country code, city code, number):
10. Office E-mail:
11. Permanent Home Address (street address, city, country, postal code):
12. Home Phone (country code, city code, number):
13. Alternative E-mail:
Applicant Certification and Acceptance
I certify that the statements herein are true, complete, and accurate to the best of my knowledge, and accept the
obligation to comply with terms and conditions if a fellowship is awarded as a result of this application. I am aware
that any false, fictitious, or fraudulent statements or claims may subject me to criminal, civil, or administrative penalties.
Applicant’s Signature
Updated 03/2014
Date
NICHD–INSERM Scholar Program
Applicant Last Name:
Mentor Last Name:
Part II—Mentor Information
1. Name of Mentor:
2. Position Title:
3. Institution:
4. Department, Division, Service, Laboratory:
5. Office Mailing Address (street address, city, state, postal code):
6. Country:
7. Office Phone (country code, city code, number):
8. Office Fax Number (country code, city code, number):
9. E-mail:
10. Alternative E-mail:
Mentor Certification and Acceptance
I certify that the statements herein are true, complete, and accurate to the best of my knowledge, and accept the obligation
to comply with terms and conditions if a fellowship is awarded as a result of this application. I am aware that any false,
fictitious, or fraudulent statements or claims may subject me to criminal, civil, or administrative penalties.
Mentor’s Signature
Date
NICHD–INSERM Scholar Program
Applicant Last Name:
Mentor Last Name:
Part III—Application Checklist
To ensure that all documents supporting the NICHD–Inserm Research Fellowship application are properly
completed and included with your application, please check the appropriate items listed below and return this
checklist with your application. Only COMPLETE applications will be reviewed.
1. Applicant To Complete and/or Provide the Following:
Form Part I and sign Certification and Acceptance Statement
Form Part III—Applicant Section
Form Parts IV and V
Form Part VI—Research Plan (not to exceed three pages, excluding literature citations)
Reference Report, Part I
Reference Report form given and reference letter has been requested from [must be two]:
1.
(Full Name of Supervisor/Colleague)
2.
(Full Name of Colleague/Supervisor)
Certification of doctoral degree(s) (including English translation if necessary)
List of peer-reviewed publications
Appendix (optional): Applicants who have authored or coauthored articles in peer-reviewed scientific journals may
submit a maximum of three publications.
2. Mentor To Complete and/or Provide the Following:
Form Part II and sign Certification and Acceptance Statement
Form Part III—Mentor Section
Form Parts VII, VIII, and IX
Form Part X and obtain necessary institution signatures as indicated
French Applicant With U.S. Mentor:
Letter from U.S. mentor’s institution representative confirming institution as a sponsor for the U.S. Department
of State “J” Exchange Visitor Program and the institution’s eligibility to prepare and issue the requisite Form
DS-2019 for the applicant and his/her dependents. The fellowship is contingent upon approval by the NIH
Division of International Services, Department of State, and the Department of Homeland Security under all
applicable immigration regulations.
 Upon acceptance of the applicant into the program, the U.S. mentor’s institution or center must submit the
required documents to the Division of International Services, Office of Research Services, National Institutes
of Health to process the request for the NIH Visiting Program: http://dis.ors.od.nih.gov/forms/01_forms.html
NICHD–INSERM Scholar Program
Applicant Last Name:
Mentor Last Name:
Part IV—Applicant’s Personal History
Add an additional page if more space is needed.
1. Education—List all postsecondary institutions you attended, beginning with the most recent.
a) Name and Location of Institution:
Major Field(s) of Study:
Begin and End Dates of Attendance (Month, Year to Month, Year):
Name of Diploma or Degree:
Date Diploma/Degree Received (Month, Year):
b) Name and Location of Institution:
Major Field(s) of Study:
Begin and End Dates of Attendance (Month, Year to Month, Year):
Name of Diploma or Degree:
Date Diploma/Degree Received (Month, Year):
c) Name and Location of Institution:
Major Field(s) of Study:
Begin and End Dates of Attendance (Month, Year to Month, Year):
Name of Diploma or Degree:
Date Diploma/Degree Received (Month, Year):
d) Name and Location of Institution:
Major Field(s) of Study:
Begin and End Dates of Attendance (Month, Year to Month, Year):
Name of Diploma or Degree:
Date Diploma/Degree Received (Month, Year):
2. Title(s) of Theses/Dissertations.
NICHD–INSERM Scholar Program
Applicant Last Name:
Mentor Last Name:
Part IV—Applicant’s Personal History (continued)
Add an additional page if more space is needed.
3. Additional Training
(include U.S. National Institutes of Health or Inserm-sponsored activities or funding)
a) Activity/Event:
Topic Field:
Institution Host/Sponsor:
Begin and End Date(s) (Month, Year to Month, Year):
b) Activity/Event:
Topic Field:
Institution Host/Sponsor:
Begin and End Date(s) (Month, Year to Month, Year):
c) Activity/Event:
Topic Field:
Institution Host/Sponsor:
Begin and End Date(s) (Month, Year to Month, Year):
4. List Your Current Employment.
Name Current Employer:
City and Country of Current Employer:
Current Job Title:
Begin and End Date(s) (Month, Year to Month, Year):
Describe your current job responsibilities:
NICHD–INSERM Scholar Program
Applicant Last Name:
Mentor Last Name:
Part IV—Applicant’s Personal History (continued)
Add an additional page if more space is needed.
5. Previous Employment.
a) Employer/Hosting Institution:
Job/Position Title:
Begin and End Date(s) (Month, Year to Month, Year):
Primary job/position responsibilities:
b) Employer/Hosting Institution:
Job/Position Title:
Begin and End Date(s) (Month, Year to Month, Year):
Primary job/position responsibilities:
c) Employer/Hosting Institution:
Job/Position Title:
Begin and End Date(s) (Month, Year to Month, Year):
Primary job/position responsibilities:
6. List your 5 to 10 most relevant peer-reviewed publications.
7. List your significant honors, awards, projects, or other accomplishments.
8. Speak to your level of proficiency in reading, speaking, and comprehending English.
NICHD–INSERM Scholar Program
Part V—Applicant’s Travel Information
Applicant Name (family name, given name, middle initial):
Date of Birth (mm/dd/yyyy):
Place of Birth (city and country):
Nationality (listed on passport):
Sex:
Passport Issued:
No
Application Pending
Yes, Expiration Date:
Issuing Country:
Traveling with Applicant during Fellowship:
Name (family name, given name, middle initial):
Relationship to Applicant (spouse, child, etc.):
Date of Birth (mm/dd/yyyy):
Place of Birth (city and country):
Nationality (listed on passport):
Sex:
Passport Issued:
No
Application Pending
Issuing Country:
Name (family name, given name, middle initial):
Relationship to Applicant (spouse, child, etc.):
Date of Birth (mm/dd/yyyy):
Place of Birth (city and country):
Nationality (listed on passport):
Sex:
Passport Issued:
No
Application Pending
Issuing Country:
Name (family name, given name, middle initial):
Relationship to Applicant (spouse, child, etc.):
Date of Birth (mm/dd/yyyy):
Place of Birth (city and country):
Nationality (listed on passport):
Sex:
Passport Issued:
No
Application Pending
Issuing Country:
Name (family name, given name, middle initial):
Relationship to Applicant (spouse, child, etc.):
Date of Birth (mm/dd/yyyy):
Place of Birth (city and country):
Nationality (listed on passport):
Sex:
Passport Issued:
No
Application Pending
Issuing Country:
Yes, Expiration Date:
Yes, Expiration Date:
Yes, Expiration Date:
Yes, Expiration Date:
NICHD–INSERM Scholar Program
Applicant Last Name:
Mentor Last Name:
Part VI—Applicant’s Research Proposal
Add an additional page if more space is needed.
1. Proposed Length of Fellowship:
12 months
24 months
2. Fellowship Goals—Provide a 50-word summary of your goals for the fellowship.
3. Research Proposal Title
4 . Research Proposal Abstract—Limit your abstract to 250 words.
5. Selection of Mentor and Institution.
Explain why you selected this mentor and institution to accomplish your research goals. Describe the key factors in
your selection. Include information about research opportunities the institution and mentor offer that may not be
available in your home country.
6. Applicant’s Full Research Plan.
Your Research Plan may not exceed three pages not including literature citations. Describe the proposed Research
Plan, including:
a) Specific aims
b) Background and significance
c) Research design and methods
d) Compliance with the applicable legal and regulatory requirements on the conduct of research at the mentor’s
institution
e) Literature citations (Each citation must include the authors’ names, book or journal titles, volume number, page
numbers, and year of publication.)
NICHD–INSERM Scholar Program
Part VII—Mentor’s Personal History
Add an additional page if more space is needed.
1. Education (Begin with baccalaureate or other initial professional education, such as nursing, and include any
postdoctoral training.)
a) Name and Location of Institution:
Degree:
Year Conferred:
Field of Study:
b) Name and Location of Institution:
Degree:
Year Conferred:
Field of Study:
c) Name and Location of Institution:
Degree:
Year Conferred:
Field of Study:
d) Name and Location of Institution:
Degree:
Year Conferred:
Field of Study:
2. List your most significant publications, honors, awards, or other accomplishments, including current
membership on a Federal Government public advisory committee.
3. How many pre- and postdoctoral fellows have you trained?
4. For a representative five of the trained pre- and postdoctoral fellows, please list their names and fellowship
training dates, current employer, and position titles.
NICHD–INSERM Scholar Program
Part VIII— French Applicant: Mentor’s Research and Training Support
Add an additional page if more space is needed.

Not applicable for U.S. Applicant
The U.S. mentor should be a NICHD researcher whose project will be active throughout the fellowship period Please
list all currently active NICHD grants or studies. Also include all applications and proposals currently pending review or
award whether related to this application or not. If any information changes after submission, immediately notify the
NICHD International Program.
Grant Source and Identifying Number:
Grant Project Title:
Principal Investigator:
Project Officer:
Mentor’s Role on Grant Project:
Percentage of Effort:
Award Date:
End Date (including no-cost extensions):
List specific aims of grant project.
Will applicant work under this grant project?
Active
Pending
Grant Source and Identifying Number:
Grant Project Title:
Principal Investigator:
Project Officer:
Mentor’s Role on Grant Project:
Percentage of Effort:
Award Date:
End Date (including no-cost extensions):
List specific aims of grant project.
Will applicant work under this grant project?
Active
Pending
Grant Source and Identifying Number:
Grant Project Title:
Principal Investigator:
Project Officer:
Mentor’s Role on Grant Project:
Percentage of Effort:
Award Date:
End Date (including no-cost extensions):
List specific aims of grant project.
Will applicant work under this grant project?
Active
Pending
NICHD–INSERM Scholar Program
Part IX—Mentor’s Statement
Add an additional page if more space is needed.
Mentor’s Statement—Submit your statement by utilizing the space below. Your statement may not exceed five pages.
Your statement should include the following:
1.
Describe the Research Plan for the applicant. Include such items as seminars and opportunities for interaction with
other groups and scientists. Describe the research environment, available research facilities and equipment, and
research support the mentor will make available to the applicant during the fellowship. Include information that will
help reviewers evaluate the applicant and the proposed research project. Indicate the relationship of the proposed
research to the applicant's career goals. Describe the skills and techniques that the applicant will learn and relate these
to the applicant’s career goals.
2. How many predoctoral and postdoctoral fellows/trainees will be supervised during the fellowship?
3. Describe the applicant’s qualifications and potential for a research career.
4. Please assess the feasibility of the Research Plan with respect to current National Institutes of Health (NIH) or Inserm
regulations on the conduct of research.
5.
Please confirm the applicant has read and understands the U.S. or French guidelines regarding the conduct of research
and agrees to comply with all NIH and other institutional requirements.
NICHD–INSERM Scholar Program
Part X—Sponsoring Institution Certifications and Assurances
1. Sponsoring Institution’s Identification Number (12-digit number) if Known (Not Applicable for French
Institutions):
2. Human Subjects:
No
Yes
If Yes, List Exemption Number or IRB Approval Date:
If Yes, List Assurance of Compliance Number:
3. Vertebrate Animals:
No
Yes
If Yes, List IACUC Approval Date:
If Yes, List Animal Welfare Assurance Number:
 Funds paid to a NICHD-funded researcher’s sponsoring institution under a NICHD–Inserm Fellowship award are
considered Federal financial assistance to that organization and must comply with the same U.S. Federal regulations,
policies, guidelines, and review considerations as do all NIH research project grant applications.
 Accordingly, the individual signing the NICHD–Inserm Fellowship application as the Official Signing for
Sponsoring Institution is certifying that the sponsoring institution and its principals will comply with all NIH as well
as Inserm terms and conditions. This signing official must be a separate individual from the mentor.
 In addition, by signing below, the mentor agrees to accept responsibility for the scientific conduct of any research
conducted as a result of a NICHD–Inserm Fellowship award and to comply with NIH, Inserm, and institutional
regulations.
 For
a complete discussion of the NIH regulations, consult the NIH Grants Policy Statement at
http://grants.nih.gov/grants/policy/nihgps_2010/index.htm or Part III, Section 2 of the U.S. Department of Health and
Human
Services,
Public
Health
Service
Grant
Application,
PHS
398
Instructions,
http://grants2.nih.gov/grants/funding/phs398/phs398.html.
 Any research conducted at NICHD or NICHD-funded institutions as a result of a NICHD–Inserm Fellowship award
must comply with all NIH policies on:
Research Using Human Embryonic Stem Cells
Human Subjects
Lobbying
Women and Minority Inclusion Policy
Inclusion of Children Policy
Vertebrate Animals
Debarment and Suspension
Recombinant DNA and Human Gene Transfer
Research
Research on Transplantation of Human Fetal Tissue
Non-delinquency on Federal Debt
Research Misconduct
Civil Rights (Form HHS 690)
Handicapped Individuals (Form HHS 690)
Sex Discrimination (Form HHS 690)
Financial Conflict of Interest
Age Discrimination (Form HHS 690)
Drug-Free Workplace
 Any research conducted at Inserm as a result of a NICHD–Inserm Fellowship award must comply with all the
internal as well as French and European applicable policies.
NICHD–INSERM Scholar Program
Applicant Last Name:
Mentor Last Name:
Part X—Sponsoring Institution Certifications and Assurances (continued)
CERTIFICATION: We, the undersigned, certify that (a) the information herein is true and complete to the best of our
knowledge; (b) if this application results in an award for a research fellowship, appropriate training, adequate facilities, and
supervision will be provided; and (c) we accept the obligation to comply with the NIH and Inserm terms and conditions of
the fellowship award. We are aware that any false, fictitious, or fraudulent statements or claims may subject us to criminal,
civil, or administrative penalties.
MENTOR
Mentor’s Name:
Email:
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Signature
Date
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UNIT OF INSERM (must be different than mentor)
Department Head or Director Name:
Email:
Office Telephone:
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Date
OFFICIAL SIGNING FOR SPONSORING INSTITUTION (For U.S. applicant, meaning the relevant Regional
Delegate at Inserm)
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NICHD–INSERM Scholar Program
List of Inserm’s Host Laboratories and Research Programs
1. Head of the Unit: Sebastian AMIGORENA, sebastian.amigorena@curie.fr
The “Immunity and Cancer” Unit of Sebastian AMIGORENA is composed of a number of team
leaders, namely Clotilde THÉRY, Claire HIVROZ, Philippe BENAROCH, Vassili SOUMELIS, Nicolas
MANEL, Olivier LANTZ and Ana-Maria LENNON DUMENIL whose research interest is indicated
below. The others team leaders are also entitled to provide or receive a scholar fellow.
Team Leader
Ana-Maria LENNON-DUMENIL
Directeur de Recherche/Research
Director
Ana-Maria.Lennon@curie.fr
Full Address
Institut Curie Inserm Unit 932
IMMUNITY AND CANCER
26 RUE D'ULM
CNRS/UMR 3215
75248 PARIS CEDEX 05
France
Research Interest:
Dendritic cells (DCs) constitute a complex cell population whose main function is to link the innate
and adaptive immune responses, thereby playing a critical role in both the establishment of
tolerance and immunity. In peripheral tissues, immature DCs continuously sample their environment
thanks to their ability to capture and process extracellular material. When encountering dangerassociated signals, DCs undergo a maturation program, which leads to the up-regulation of CCR7
expression. This chemokine receptor allows the recognition of a CCL21 haptotactic gradient,
resulting in an important migratory flow of DCs to lymph nodes, where they activate T cells and
thereby launch the adaptive immune response. Defining how DC migration is regulated in both
homeostatic and inflammatory conditions is therefore essential to understand how they link innate to
adaptive immunity.
The general goal of the present proposal is to use a bottom-up approach that combines cell biology,
immunology and micro-fluidics in order to (1) determine how dendritic cell migration is regulated by
their microenvironment in tissues and (2) to evaluate the impact of such regulation on the adaptive
immune response. We will focus on both physical and biochemical extracellular cues known to vary in
the DC microenvironment between homeostatic and inflammatory conditions: the extracellular
hydrostatic pressure and the composition of the extracellular matrix (ECM).
2. Head of the Unit: Edith HEARD, edith.heard@curie.fr
The “Genetics and Development Biology” Unit of Edith HEARD is composed of a number of team
leaders, namely Deborah BOURC’HIS, Filippo DEL BENE, Silvia FRE, Jean Rene HUYHN, Raphael
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MARGERON, Anna SHKUMATAVA and Yohanns BELLAICHE whose research interest is indicated
below. The others team leaders are also entitled to provide or receive a scholar fellow.
Team Leader
Yohanns BELLAICHE
yohanns.bellaiche@curie.fr
Directeur de recherche/Research
Director
Full Address
Institut Curie Inserm Unit 934
Genetics and Development Biology
26 rue d'ulm
CNRS/UMR 3215
75248 paris cedex 05
France
Research Interest:
Questions related to embryo shape or morphogenesis have naturally haunted developmental
biologists for decades. We aim to understand the conserved mechanisms that regulate the
morphogenesis of proliferative epithelial tissue. To this end, we are applying a series of
complementary state of the art methods: advanced light microscopy, quantitative measurement
of cell and tissue morphogenesis, mechanical stress inference, opto-genetics, computer
simulation and advanced statistics in order to:
1. Dissect the mechanisms regulating cytoskeleton and cell dynamics by focusing on mitotic
spindle orientation and de novo adherens junction formation during cell division.
2. Link cytoskeleton organization, cell dynamics and mechanics to the regulation of large-scale
tissue deformation.
3. Introduce a ‘morphogenomics’ approach to understand how combinatory gene expression
patterns can account for distinct cell dynamics observed in the different regions of a tissue.
By exploring the mechanisms of tissue morphogenesis at different time-scales and lengthscales, as well as by focusing both on its genetic and mechanical regulation, these
complementary aims should advance the understanding of morphogenesis in animals.
3. Head of the Unit : Ludger JOHANNES, ludger.johannes@curie.fr
Laboratory:
Institut Curie
Research Unit INSERM U1143-CNRS UMR3666
Chemical Biology of Membranes and Therapeutic Delivery
26 RUE D'ULM
CNRS/UMR 3215
75248 PARIS CEDEX 05 France
https://perso.curie.fr/Ludger.Johannes/
Research Interest:
In the Endocytic Trafficking and Intracellular Delivery team we study the cell biology of
carbohydrate-binding proteins (lectins) in the context of cellular entry though clathrin-independent
endocytosis, retrograde sorting on early endosomes, and membrane translocation to the cytosol.
We hypothesize that certain lectins link glycosylated cargo proteins and glycosphingolipids into
molecular nanoenvironments from which endocytic pits are formed in a process that is
independent of the cytosolic clathrin machinery. Our current efforts are geared at unraveling the
mechanistic and functional framework of this novel concept in membrane biology, notably also
using chemical biology tools to rebuild this process (synthetic biology). Another focus of our work
is based on our pioneering discovery of the early endosomes — TGN retrograde trafficking
interface. We now analyze possible molecular and functional links between endocytic sorting at
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the plasma membrane and retrograde sorting on early endosomes. Finally, we explore the
process of endosomal escape to the cytosol from a mechanistic and biomedical perspective in an
attempt to device innovative strategies of therapeutic delivery and immunotherapy for the
treatment of tumor pathologies.
4. Head of the Unit : Antoine TRILLER, triller@biologie.ens.fr
Laboratory:
Biologie Cellulaire de la Synapse N&P
IBENS, Institut de Biologie de L'ENS
Ecole Normale Supérieure
46, rue d'Ulm 75005 Paris - FRANCE
http://www.ibens.ens.fr/
http://www.biologie.ens.fr/bcsnp/
Research Interest:
Our aim is to determine key aspects of the relationship between the synapse microstructure,
molecular dynamics, and molecular interactions. More precisely we want to establish the link
between diffusion dynamic and receptor trapping at synapses in relation with molecular
interactions. This will posit the mechanisms responsible for receptor accumulation at synapses,
and its regulations. We now want: 1) to establish how phosphorylation-dependent affinities within
the postsynaptic assembly impact the diffusion dynamics and number of receptors at synapses;
and 2) to link this regulation with excitation/inhibition equilibrium. To achieve these aims we are
now implementing novel super-resolution imaging methods (PALM, STORM, STED microscopy,
adaptive optics), single molecule tracking (3D-PALM, PALM-SPT) and specific analytical
approaches using tools developed by physicists combined with electro-physiology.
In parallel, we are exploring other aspects of synapse functions:
• Non-cell autonomous regulation of inhibitory synapses: glia and inflammation with emphasis on
microglia modulation of receptor diffusion-trapping and impact on neuronal excitability.
• Human synapse specificity: The partial duplications of SRGAP2 in the human lineage have
contributed to the humanization of dendritic spines by a mechanism that relies on the inhibition of
the ancestral protein by its human-specific copy. We now employ single cell in vivo manipulations
of gene function as well as molecular imaging techniques to investigate the cellular and molecular
bases underlying the humanization of synapse development and plasticity
5. Head of the Unit : Pierre Olivier COURAUD,
pierre-olivier.couraud@inserm.fr
The Unit of Pierre Olivier Couraud is a Research Center organized in 3 scientific
departments:Endocrinology, metabolism and Diabetes (EMD); Infection, Immunity and Inflammation
(3I); Development, Reproduction and Cancer (DRC). The reserach interst of 3 team Leaders are
indicated below, namely of Daniel VAIMAN, Sandrine BOURDOULOUS and Raphael
SCHERFMANN. The others team leaders are also entitled to provide or receive a scholar fellow.


Team Leaders
Daniel VAIMAN
daniel.vaiman@inserm.fr
Sandrine BOURDOULOUS, Team:
Vascular Cell Biology
Full Adress
Institut Cochin Inserm
Unit 1016
22 rue Méchain, 75014
Paris - France
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
sandrine.bourdoulous@inserm.fr
Raphael Scharfmann
Raphael.scharfmann@inserm.fr
Research Interest:
«Genomics, Epigenetics and Physiopathology of Reproduction», Daniel Vaiman’s team. This
team of 35 members is an integrative structure at the interface of clinical and fundamental studies of
human reproduction disorders. The research programs developed in the team aim at deciphering
the scientific grounds of various aspects of reproductive physiology and at elucidating the
pathophysiological mechanisms involved in the most frequent reproductive diseases. Among these
diseases are, on the one hand, male/female infertility resulting from defects of sperm differentiation,
ovary function, sperm maturation, sperm-oocyte interaction or defects of implantation and, on the
other hand, pregnancy diseases affecting the mother and/or the foetus and resulting from defects of
embryonic implantation, uterine dysfunction or extra-embryonic tissue development anomalies
http://cochin.inserm.fr/departments/drc/team-vaiman.
Bacterial interaction with the microvasculature, a target for therapeutic intervention during
septicaemia, Sandrine Bourdoulous team
Bacterial septicaemia remains a prominent cause of death in developed countries. An essential
feature in the pathogenesis of invasive systemic bacteria is their ability to interact with the
microvasculature, which allows dissemination, local activation of coagulation pathways and vascular
leakage. Paradoxically, these aspects remain poorly explored. Among major issues to be solved are
the host molecular and cellular events leading to vascular dysfunction, thrombosis, organ failure and
immune escape by these bacterial pathogens.
Neisseria meningitidis (meningococcus) is an example of invasive bacterial pathogen responsible
for dissemination into different organs including meninges and skin. Specific interaction of this
bacterium with the human microvasculature is responsible for thrombotic lesions, which, in the most
extreme cases, lead to purpura fulminans, a life-threatening syndrome associating septic shock with
vascular leakage and extensive thrombosis leading to death in 30% of the patients.
Taking N. meningitidis as a paradigm for invasive extracellular pathogens interacting with human
microvessels, our goal is to integrate high throughput sequencing methods, combined with
molecular, immunological and imaging approaches, to decipher the initial events of meningococcal
infection in vivo and to understand the mechanisms by which this pathogen subverts the innate
immune response and adapts to the human host. Our ultimate objective is to define new therapeutic
strategies to prevent the dramatic consequences of meningococcal interaction with the
microvasculature, in order to improve the efficiency of medical intervention and reduce deaths and
severe sequelae.
Pancreatic Beta Cell Development: A roadmap to generate and study functional human beta
cells, Raphael Scharfmann team
Pancreatic beta cells develop from endodermal pancreatic progenitors that first proliferate and next
differentiate into functional insulin-producing cells. This developmental process is complex, each
step being controlled by yet unknown signals. Theoretically, the development of a functional beta
cell mass can be enhanced by: i) activating the proliferation of pancreatic progenitors; ii) activating
their differentiation into beta cells; iii) activating the proliferation of beta cells themselves.
During the past years, we first developed bioassays based on rodent models to search for signals
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that control specific steps of beta cell development. With such bioassays, we screened and
characterized a number of signals that regulate pancreatic progenitor cell proliferation and
differentiation. We also developed models of human pancreatic development, to transfer to human,
data generated in rodent models. Such models were instrumental for the development of functional
human beta cell of lines (1, 2).
We are currently using such lines to better dissect the regulation of functional beta cell mass in
patho-physiological conditions (3).
References:
-1- Ravassard P, Hazhouz Y, Pechberty S, Bricout-Neveu E, Armanet M, Czernichow P,
Scharfmann R. A genetically engineered human pancreatic β cell line exhibiting glucose-inducible
insulin secretion. J Clin Invest. 2011 121:3589-97.
-2- Scharfmann R, Pechberty S, Hazhouz Y, von Bülow M, Bricout-Neveu E, Grenier-Godard
M, Guez F, Rachdi L, Lohmann M, Czernichow P, Ravassard P. A conditionally immortalized human
pancreatic beta cell line. J Clin Invest 2014, 124:2087-98
-3- Chandra V, Albagli-Curiel O, Hastoy B, Piccand J, Randriamampita C, Vaillant E, Cavé
H, Busiah K, Froguel P, Vaxillaire M, Rorsman P, Polak M, Scharfmann R. RFX6 Regulates Insulin
Secretion by Modulating Ca2+ Homeostasis in Human Beta Cells. Cell Rep. 2014 9:2206-18
6. Head of the Unit : Alain PROCHIANTZ,
alain.prochiantz@college-de-france.fr
Team Leader
Marie-Hélene VERLHAC, mariehelene.verlhac@college-de-france.fr
Full Address
CIRB, Collège de France
11 place Marcelin Berthelot
75231 Paris Cédex 05
Research Interest:
Asymmetric Divisions in Oocytes
Oocytes divide asymmetrically forming a large cell, the oocyte and two small ones, the polar
bodies. These asymmetric divisions allow maternal stores to be retained in the oocyte for further
embryo development and are ensured by actin-based positioning of the acentrosomal and
anastral meiotic spindle. In mitotic cells, the centrosomes, with its astral microtubules contacting
the cortex, acts as a sensor of cell geometry and as an integrator to orient cell division. We are
interested in the way mouse meiotic spindles are built and positioned in the absence of canonical
centrosomes. We would like to answer the following questions: which pathways control meiotic
spindle assembly in the absence of canonical centrosomes? How the actin-based spindle
positioning process is regulated? Is there a coupling of spindle morphogenesis and positioning?
How is it performed? How is the symmetry of the oocyte, initiating the process with no sign of
polarity, broken to ensure asymmetric divisions? What would happen if we could engineer
oocytes to add back centrioles to these cells?
7. Head of the Unit : Serge CHARPAK, serge.charpak@parisdescartes.fr
The “Neurophysiology & New Microscopies Laboratory” of Serge Charpak is composed of a number
of team leaders, including Etienne AUDIMAT, Maria Cecilia ANGULO and Serge CHARPAK whose
research interest is indicated below. The others team leaders are also entitled to provide or receive a
scholar fellow.
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Team Leader
Serge CHARPAK,
serge.charpak@parisdescartes.fr
Full Address
CENTRE UNIVERSITAIRE DES SAINTS PERES
Inserm Unit 1128
Neurophysiology & New Microscopies Laboratory
CNRS UMR 8154
3rd Floor - 45 rue des Saints Pères
75006 PARIS - France
Research Interest:
« From sensory processing to functional hyperaemia »
Our goal is to understand how a sensory stimulus such as an odor generates a population activity in
a small cellular network, the olfactory bulb glomerulus.
We investigate this question by using or developing optical tools based on two-photon microscopy
that can be combined with electrophysiological recordings and allow the observation of neuron and
astrocyte activity in vitro and in vivo.
During the last 5 years, our research aimed in three directions:
• The improvement of optical methods to image cellular activity, blood flow and brain metabolism
• The study of synaptic interactions within the glomerular network
The analysis of neurovascular coupling, functional hyperaemia and energy consumption in glomeruli
8. Head of the Unit : Jean Louis MARTIN, jean-louis.martin@polytechnique.edu
Team Leader
Dr François HACHE
Directeur du Laboratoire d'Optique et
Biosciences – CNRS UMR7645/INSERM
U1182/Ecole
Polytechnique
Département
d'Enseignement-Recherche de Physique
- Ecole Polytechnique
Ecole Polytechnique
91128 Palaiseau - France Tel (+33) 1 69 33 50 39
francois.hache@polytechnique.edu
Full Address
Laboratoire d'Optique et
Biosciences
INSERM U696 - CNRS UMR7645
Aile 2, Niveau 2 (1er étage)
Ecole Polytechnique
91128 PALAISEAU Cedex - France
http://www.lob.polytechnique.fr/jsp/
accueil.jsp?CODE=08752645&LAN
GUE=1
Research Interest:
The Laboratory for Optics and Biosciences gathers biologists and physicists to come up with new
investigation techniques on relevant biophysical issues. Among the research activities of the
laboratory, let us cite the "Advanced microscopy and tissue physiology" group which develops
novel experimental approaches based on a solid expertise in nonlinear optics and in tissue
microscopy. The aim is to study in situ the links between cell physiology and tissue adaptation in
contexts such as embryo morphogenesis, nervous system development, and extracellular matrix
remodeling. Two complementary aspects are pursued (i) method developments / proof-ofprinciple studies, and (ii) their application to novel biomedical issues, through an active
collaboration network. Another group "Nano-imaging and cell dynamics" focusses on the
investigation of cell dynamics using nano-imaging tools that include nanolabels, nanosensors,
and microfluidic technology for controlled cell stimulation. They study spatio-temporal
organization of signaling pathways, in the membrane organization and its role in signaling and in
toxin-cell interactions.
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9. Head of the Unit : Bertrand SERAPHIN, directeur.igbmc@igbmc.fr
IGBMC - Institut de Génétique et de
Biologie Moléculaire et Cellulaire
IGBMC - CNRS UMR 7104 - Inserm U 964
1 rue Laurent Fries / BP 10142 / 67404
Illkirch CEDEX / France
http://www.igbmc.fr/research/
Research Interest:
The Institute of Genetics and Molecular and Cellular Biology (IGBMC), located in the
Strasbourg Eurométrople, is now one of the main European research centers in biomedical
research and the largest French research unit associated to the Inserm. The IGBMC is
structured around 4 scientific departments and advanced scientific services and technological
platforms. The Institute develops interdisciplinary research at the interface of biology,
biochemistry, physics and medicine.
Among the research lines developed at IGBMC, analyses of early development and the
deciphering of cellular functions are addressed by several teams. Several model organisms
including mouse, drosophila, C. elegans, yeast as well as cultured mammalian cells serve as a
basis for these analyses. The use of mice is particularly developed thanks to the location on site
of the Mouse Clinical Institute, a main European facility for mice genetic engineering and
standardized functional analysis.
Additional facilities including an internationally recognized Imaging center including advanced
optical imaging, high-resolution electron microscopy and image analyses facilitate the work of
research teams. Further information on the institute, the team’s scientific projects and support
facilities is available on the web site: http://www.igbmc.fr
10. Head of the Unit : Pierre HAINAUT, Pierre.Hainaut@ujf-grenoble.fr
The “Ontogenèse et Oncogenèse Moléculaires” Unit of Pierre HAINAUT is composed of a number of
team leaders, including Saadi KHOCHBIN, Elisabeth BRAMBILLA and Corinne ALBIGES RIZO
whose research interest is indicated below. The others team leaders are also entitled to provide or
receive a scholar fellow.
Team Leader
Corinne ALBIGES RIZ0,
corinne.albiges-rizo@ujf-grenoble.fr
Full Address
INSTITUT ALBERT BONNIOT Centre de
Recherche U823 - "Ontogenèse et
Oncogenèse Moléculaires" INSERM – UJF
Site Santé, BP 170 - La Tronche - 38042
GRENOBLE Cedex 9 - FRANCE
http://www-iab.ujfgrenoble.fr/index.php?b=1&c=11
Research Interest:
My team is working on how cells perceive their microenvironment by sensing chemical, physical
and mechanical cues of extracellular matrix through integrin-based adhesive machineries and
actomyosin-based contractility. We are interested in dynamics of adhesive structures named
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focal adhesion and invadosomes. These mechanosensitive actin-based adhesive structures are
known to be different in architecture, dynamics and function even though they share almost the
same proteins. Our hypothesis is that such pivotal cellular decisions depend on the precise
temporal control and relative spatial distribution of pleiotropic molecules rather than their simple
activation or inhibition. We addressed the question of how such pleiotropic molecules can induce
the formation and the disorganization of such different actin-based adhesion structures. Our
project is to use photoactivation and optogenetic tools to analyse dynamics of adhesive
molecules and to control their membrane localization in space and time (Cry2-Cibn strategy,
SPT, TIRF, FCS, RICS and spinning disk) in the hope of generation of specific adhesive
structures. These different spation Force Microscopy).
11. Head of the Unit : Stephane NOSELLI, stephane.noselli@unice.fr
Institut de Biologie Valrose, iBV
UMR7277 CNRS - UMR1091 INSERM
Université de Nice Sophia-Antipolis
Parc Valrose
06108 NICE cedex 2
FRANCE
http://ibv.unice.fr/EN/index.php
Research Interest:
New genes and mechanisms involved in Left-Right asymmetry in Drosophila and zebrafish
Breaking left-right (LR) symmetry in Bilateria embryos is a major event in body plan
organization. Both in vertebrates and invertebrates, the establishment of LR asymmetry is essential
for handedness, directional looping of internal organs (heart, gut...) and differentiation of the heart
and brain. Abnormal LR patterning during embryogenesis leads to a number of defects and
syndromes including congenital heart diseases, spontaneous abortion, asplenia, polysplenia,
Kartagener and Ivemark syndromes etc..
Our laboratory pioneered the study of LR asymmetry in Drosophila and identified several
major genes controlling organ looping and LR morphogenesis. The conserved MyosinID gene
(MyoID) was identified as a major LR determinant in flies, which is required for dextral coiling of
organs. In the absence of MyoID, flies show a situs inversus phenotype and organs undergo
sinistral morphogenesis. Recently we identified the conserved HOX gene Abdominal-B as a major
upstream factor controlling MyoID expression and LR asymmetry establishment.
Our current work addresses two mains questions: what are the molecular partners of MyoID
and Abd-B in controlling LR asymmetry? Is MyoID function conserved in vertebrates? To address
the first question we are running genetic and molecular screens. Several interesting candidates are
currently under study providing new insights into the molecular mechanisms leading to symmetry
breaking and cell/organ morphogenesis.
To test if MyoID is conserved in vertebrates, we are currently performing experiments using
zebrafish. Preliminary results indicate a conservation of MyoID in this model, opening up new
exciting avenues on possible unifying mechanisms in vertebrates and invertebrates.
Several potential new projects will be proposed based on current results. Work in the
laboratory is highly interactive and collaborative.
Publications on LR asymmetry from the lab: Adam et al., Development 2003 ; Spéder et al.,
Nature 2006; Hozumi et al., Nature 2006 ; Spéder & Noselli, Curr. Opin. Cell Biol. 2007 ; Spéder et
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al., Curr. Opin. Genet. Dev. 2007 ; Coutelis et al., Sem. Cell Dev. Biol., 2008 ; Suzanne et al., Curr.
Biol. 2010 ; Petzoldt et al., Development 2012 ; Coutelis et al., Developmental Cell, 2013. Géminard
et al. Genesis, 2014 ; Coutelis et al., EMBO Reports, 2014 ; Gonzalez-Morales et al. Developmental
Cell, 2015 (in press).
Training:
Candidates will be trained in molecular biology and genetics/transgenesis, cell biology, imaging etc..
Work will be performed at institute de Biologie Valrose, iBV, a leading Biology institute in Nice (with
highest AERES ranking: 5 A+). iBV is an internationally recognized institute (English is the working
language; 25 different nationalities hosted) with state-of-the-art facilities.
12. Head of the Unit : Chantal VAURY-ZWILLER, chantal.vaury@udamail.fr, chantal.
vaury@inserm.fr
The “Génétique Reproduction & Développement” Unit of Chantal VAURY-ZWILLER is composed of a
number of team leaders, including Joel DREVET and Claire CHAZAUD whose research interest is
indicated below. The others team leaders are also entitled to provide or receive a scholar fellow.
Team Leader
Dr. Claire Chazaud, PI
at GReD,
claire.chazaud@udama
il.fr
Full Address
GReD - Génétique Reproduction & Développement
Inserm Unit 1103 - CNRS/UMR6293
Faculté de Médecine
28, place Henri Dunant
BP 38 - 63001 CLERMONT-FERRAND
France
https://www.gred-clermont.fr/
Research Interest:
Stems cells of the embryo: molecular mechanisms of cell lineage differentiation.
Our team is interested in deciphering the molecular mechanisms regulating cell differentiation during
mouse embryogenesis. We are focusing on the binary specification of epiblast (Epi) and Primitive
Endoderm (PrE) within the Inner Cell Mass of the blastocyst during preimplantation. The cells that
constitute the foetus are descendants from the Epi, a pluripotent embryonic tissue that is the source
of the Embryonic Stem (ES) cells. Thus our projects are deeply connected to Stem Cell research.
We have recently described the role of Nanog (Frankenberg et al, 2011 Dev Cell) and Gata6
(Bessonnard et al, 2014 Development) to show that the balance between these two transcription
factors, modulated by the ERK pathway, determines the number and the timing of Epi and PrE cells
specification. In collaboration, these results enabled us to build a mathematical model (Bessonnard
et al, 2014 Development), uncovering novel features that we are now exploring.
We are also looking for upstream and downstream factors of this core network using different tools
(single cell transcriptomics, transgenics, live imaging...) in ES cells and embryos.
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List of NICHD’s Host Laboratories and Research Programs
at the National Institutes of Health
Bethesda, Maryland 20892 USA
1.
Section Head
Juan Bonifacino
Section on Intracellular Protein Trafficking
Address
Email: BonifacinoJ@mail.nih.gov
Phone: 301-496-6368
Bldg 35A, Rm 2F-226
Research Interest:
Protein Sorting in the Endosomal-Lysosomal System
We investigate the molecular mechanisms by which transmembrane proteins are sorted to different
compartments of the endomembrane system such as endosomes, lysosomes, and a group of cell
type–specific organelles known as lysosome-related organelles (e.g., melanosomes and platelet
dense bodies). Sorting is mediated by recognition of signals present in the cytosolic domains of the
transmembrane proteins by adaptor proteins that are components of membrane coats (e.g.,
clathrin coats). Among these adaptor proteins are the heterotetrameric AP-1, AP-2, AP-3, and AP4 complexes, the monomeric GGA proteins, and the heteropentameric retromer complex. Proper
sorting requires the function of additional components of the trafficking machinery that mediate
vesicle tethering and fusion. Current work in our laboratory is aimed at elucidating the structure,
regulation, and physiological roles of coat proteins and vesicle-tethering factors and investigating
human diseases that result from genetic defects (e.g., Hermansky-Pudlak syndrome and
neurodegenerative and neurodevelopmental disorders) in these proteins.
Biography
Dr. Juan Bonifacino received his doctoral degree in biochemistry from the University of Buenos
Aires, Argentina, in 1981. He then moved to the NIH, where he pursued postdoctoral studies with
Dr. Richard D. Klausner. He rose through the ranks, eventually becoming the Head of the Cell
Biology and Metabolism Program. In 2008, he was appointed NIH Distinguished Investigator. Since
the early 1990s, Dr. Bonifacino's group has conducted research on signals and adaptor proteins
that mediate protein sorting to endosomes and lysosomes. His group discovered new sorting
signals and adaptor proteins, and applied this knowledge to the elucidation of the causes of
various human diseases including the Hermansky-Pudlak syndrome type 2 and autosomal
dominant polycystic liver disease. Dr. Bonifacino has served in various editorial capacities for
journals including Developmental Cell, Molecular Cell, Molecular Biology of the Cell, Journal of Cell
Biology, Journal of Biological Chemistry and Traffic. He is also the co-editor of the books Current
Protocols in Cell Biology and Short Protocols in Cell Biology. He has served as a member of the
Council of the American Society for Cell Biology and chaired various scientific conferences. He has
delivered the Alex Novikoff, Leonardo Satz, George Connell and G. Burroughs Mider lectures, and
is an Honorary Professor of Biological Chemistry at the University of Buenos Aires and a Sackler
Lecturer at Tel Aviv University, Israel. His lab has trained over 70 postdoctoral fellows and
5|Page
students, most of whom have pursued careers in academic research.
2.
Section Head
Mary Lilly
Section on Gamete Development
Address
Email: MLilly@helix.nih.gov
Phone: 301-435-8428
Bldg 32T11 Rm 101
Research Interest:
Cell Cycle Regulation in Oogenesis
The long-term goal of our laboratory is to understand how the cell-cycle events of meiosis are
coordinated with the developmental events of gametogenesis. Chromosome mis-segregation
during female meiosis is the leading cause of miscarriages and birth defects in humans. Recent
evidence suggests that many meiotic errors occur downstream of defects in oocyte growth and/or
the hormonal signaling pathways that drive differentiation of the oocyte. Thus, an understanding of
how meiotic progression and gamete differentiation are coordinated during oogenesis is essential
to studies in both reproductive biology and medicine. We use the genetically tractable model
organism Drosophila melanogaster to examine how meiotic progression is both coordinated
with and instructed by the developmental program of the egg.
In mammals, studies on the early stages of oogenesis face serious technical challenges in that
entry into the meiotic cycle, meiotic recombination, and the initiation of the highly conserved
prophase I arrest all occur during embryogenesis. In contrast, in Drosophila these critical events
of early oogenesis all take place continuously within the adult female. Easy access to the early
stages of oogenesis, coupled with the available genetic and molecular genetic tools, makes
Drosophila an excellent model for studies on meiotic progression and oocyte development.
To understand the regulatory inputs that control early meiotic progression, we are working to
determine how the oocyte initiates and then maintains the meiotic cycle within the challenging
environment of the ovarian cyst. Our studies focus on questions that are relevant to the
development of all animal oocytes. What strategies does the oocyte use to protect itself from
inappropriate DNA replication? How does the oocyte inhibit mitotic activity before meiotic
maturation and the full growth and development of the egg? How does cell-cycle status within the
ovarian cyst influence the differentiation of the oocyte? To answer these questions, we have
undertaken studies to determine the basic cell-cycle program of the developing ovarian cyst.
Biography
Dr. Mary Lilly received her Ph.D. in Biology from Yale University. In 1992 she joined the laboratory
of Dr. Allan Spradling at the Carnegie Institution of Washington, Department of Embryology, for her
postdoctoral training. Dr. Lilly was recruited to the Cell Biology and Metabolism Branch of NICHD
in 1998. Currently she is the head of the Section on Gamete Development.
6|Page
3.
Section Head
Jennifer Lippincott Schwartz
Section on Organelle Biology
Address
Email: Lippincj@mail.nih.gov
Phone: 301-402-1009
Bldg 35A, Rm 2F-220
Research Interest:
Dynamics of Membrane Trafficking, Sorting, and Compartmentalization Within Eukaryotic
Cells
We investigate the global principles underlying secretory membrane trafficking, sorting, and
compartmentalization within eukaryotic cells. We use live-cell imaging of green fluorescent protein
(GFP) fusion proteins in combination with photobleaching and photoactivation techniques to
investigate the subcellular localization, mobility, transport routes, and turnover of a variety of
proteins with important roles in the organization and regulation of membrane trafficking and
compartmentalization. To test mechanistic hypotheses about protein and organelle dynamics, we
use quantitative measurements of these protein characteristics in kinetic modeling and simulation
experiments. Among the topics under investigation are (i) membrane partitioning and its role in
protein sorting and transport in the Golgi apparatus; (ii) biogenesis and dynamics of
unconventional organelles; (iii) mitochondrial morphology and its regulation of cell cycle
progression; and (iv) cytoskeletal and endomembrane cross-talk in polarized epithelial cells,
hematopoietic niche cells, and the developing Drosophila syncytial blastoderm embryo. We also
devoted considerable effort to developing new fluorescence microscopy techniques for imaging
fluorescently
tagged
proteins
at
near-molecular
resolution.
Biography
Dr. Jennifer Lippincott-Schwartz obtained her Ph.D. from Johns Hopkins University in Baltimore,
MD and received postdoctoral training with Dr. Richard Klausner of NICHD. She is currently Chief
of the Section on Organelle Biology in the Cell Biology and Metabolism Branch of the NICHD. Dr.
Lippincott-Schwartz's research uses live cell imaging approaches to analyze the spatio-temporal
behavior and dynamic interactions of molecules in cells. These approaches have helped to change
the conventional “static” view of protein distribution and function in cells to a more dynamic view
that integrates information on protein localization, concentration, diffusion, and interactions that are
indiscernible from protein sequences and in vitro biochemical experiments alone. The projects in
Lippincott-Schwartz's lab cover a vast range of cell biological topics, including protein transport and
the cytoskeleton, organelle assembly and disassembly, and the generation of cell polarity. Analysis
of the dynamics of fluorescently labeled proteins expressed in cells is performed using numerous
live cell imaging approaches, including FRAP, FCS, and photoactivation. Most recently, her
research has focused on the development and use of photoactivatable fluorescent proteins, which
“switch on” in response to uv light. One application of these proteins she has put to use is in
photoactivated localization microscopy (i.e., PALM), a superresolution imaging technique that
enables visualization of molecule distributions at high density at the nano-scale. Dr. LippincottSchwartz serves as Editor for Current Protocols in Cell Biology and The Journal of Cell Science
and she is on the editorial boards of Cell, Physiology, and Molecular Biology of the Cell. She is an
active member of the scientific community, having served as a member of the Council for the
American Society of Cell Biology and on the Executive Board of the Biophysical Society. She was
elected to the National Academy of Sciences in 2008 and the National Institute of Medicine in
2009.
7|Page
4.
Section Head
Gisela Storz
Section on Environmental Gene
Regulation
Address
Bldg 18, Rm 113
Phone: 301-402-0968
Email: Storzg@mail.nih.gov
Research Interest:
Small Regulatory RNAs and Small Proteins
Currently, we have two main interests: the identification and characterization of small noncoding
RNAs and the identification and characterization of small proteins of less than 50 amino acids. For
two reasons, small RNAs and small proteins have been overlooked. First, biochemical assays do
not detect these small molecules. Second, genome annotation misses the corresponding genes,
which are poor targets for genetic approaches. However, mounting evidence suggests that both
classes of these small molecules play important regulatory roles.
Biography
Dr. Gisela Storz is the Deputy Chief of the Cell Biology and Metabolism Program of NICHD. She
received her Ph.D. from the University of California, Berkeley, and then carried out postdoctoral
work at the National Cancer Institute and Harvard Medical School. For many years, a major focus
of her group was the study of the bacterial and fungal responses to oxidative stress and redoxsensitive transcription factors. Her lab made the exciting discovery that the activity of the E. coli
transcription factor OxyR is regulated by reversible disulfide bond formation, establishing a
paradigm for redox-sensing proteins. As a result of the serendipitous detection of the peroxideinduced OxyS RNA, one of the first small, regulatory RNAs to be discovered, work in her lab
shifted to the genome-wide identification of small RNAs. The pioneering characterization of many
of these small RNAs revealed that they are integral to most regulatory circuits in bacteria.
Recently, work in the Storz lab has extended to the detection and characterization of proteins of
less than 50 amino acids, another class of molecules that is overlooked by traditional methods of
investigation.
5.
Section Head
Harold Burgess
Unit on Behavioral Neurogenetics
Address
Email: HaroldBurgess@mail.nih.gov
Phone: 301-402-6018
Bldg 6B, Rm 3B308
Research Interest:
Neuronal
Circuits
Controlling
Behavior:
Genetic
Analysis
in
Zebrafish
Our goal is to understand how neuronal circuits in larval zebrafish produce appropriate motor
responses under diverse environmental contexts. Locomotor behavior in zebrafish larvae is
controlled by neuronal circuits that are established through genetic interactions during
development. We aim to identify genes and neurons that are required for the construction and
function of the brainstem circuits underlying specific behaviors. Neuronal circuits situated
8 | P aing ethe
brainstem form the core of the locomotor control network in vertebrates and are responsible
for balance, posture, motor control, and arousal. Accordingly, many neurological disorders stem
from abnormal formation or function of brainstem circuits. Insights into the function of brainstem
circuits in health and disease have come from genetic manipulation of neurons in zebrafish larvae,
in combination with computational analysis of behavior.
Several unique features of the zebrafish model system facilitate analysis of the neuronal basis
of vertebrate behavior. The larval zebrafish brain exhibits the basic architecture of the vertebrate
brain but is much less complex than the mammalian brain. The optical clarity of the embryo
facilitates visualization of individual neurons and their manipulation with genetic techniques.
Behavior in larvae is innate and therefore exhibits minimal variability between fish. Subtle
alterations in behavior can therefore be robustly scored, making it possible to assess quickly the
contribution of identified neurons to a variety of motor behaviors. We use two major behavioral
paradigms to investigate the neuronal basis of vertebrate behavior: modulation of the acoustic
startle response by prepulse inhibition and modulation of the locomotor repertoire during a
phototaxis-based navigational task. In addition, we are developing a suite of genetic tools and
behavioral assays to probe the nexus between neuronal function and behavior at single-cell
resolution.
Biography
Dr. Harold Burgess received his B.S. from the University of Melbourne, Australia and his Ph.D.
from the Weizmann Institute of Science, Israel studying molecular interactions underlying cortical
development. He did postdoctoral training with Dr. Michael Granato at the University of
Pennsylvania, where he developed computational tools for high throughput analysis of behavior in
larval zebrafish. Dr. Burgess joined NICHD as an investigator in 2008. His laboratory now
combines genetic and imaging techniques to study neural circuits required for sensory guided
behavior in zebrafish.
6.
Section Head
David Clark
Section on Chromatin and Gene
Expression
Address
Bldg 6A, Rm 2A14
Phone: 301-496-6966
Email: Clarkda@mail.nih.gov
Research Interest:
Chromatin
Remodeling
and
Gene
Activation
Gene activation involves the regulated recruitment of factors to a promoter in response to
appropriate signals, ultimately resulting in the formation of an initiation complex by RNA
polymerase II and subsequent transcription. These events must occur in the presence of
nucleosomes, which are compact structures capable of blocking transcription at every step. To
circumvent the chromatin block, eukaryotic cells possess chromatin-remodeling and nucleosomemodifying complexes. The former (e.g., the SWI/SNF complex) use ATP to drive
conformational changes in nucleosomes and to slide nucleosomes along DNA. The latter contain
enzymatic activities (e.g., histone acetylases) that modify the histones post-translationally to mark
them for recognition by other complexes. Our previous work using native plasmid chromatin from
the yeast Saccharomyces cerevisiaerevealed that activation correlates with 9large-scale
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movements of nucleosomes and conformational changes within nucleosomes over entire genes.
Using paired-end sequencing, we have now confirmed and extended these observations by
determining nucleosome positions genome-wide. In addition, we discovered that, unlike
canonical nucleosomes, the centromeric nucleosome, which contains a specialized histone
(Cse4/CenH3), is perfectly positioned. Our current work focuses on the roles of chromatinremodeling machines in nucleosome positioning and gene activation.
Biography
Dr. David Clark has worked in the chromatin field since graduate school and completed a PhD with
Professor Jean Thomas in Cambridge to address the mechanism of chromatin folding by the linker
histone, H1. As a postdoctoral fellow in Dr. Gary Felsenfeld's laboratory at the NIH, Dr. Clark
studied the problem of how RNA polymerase transcribes through a nucleosome. The nucleosome
is a highly compact structure and a potent barrier to transcription. The lab was very interested in
the proposal that a transcribing polymerase is preceded by positive supercoils with negative
supercoils in its wake. Since the nucleosome contains negatively supercoiled DNA, it seemed
possible that positive supercoils would destabilize nucleosomes ahead of the transcribing
polymerase. Although the lab found that nucleosomal structure is surprisingly resistant to positive
superhelical stress, it also observed that nucleosomes are relatively unstable on positively
supercoiled DNA and therefore possess a latent tendency for transfer to negatively supercoiled
DNA. The lab proposed that RNA polymerase might exploit this tendency during transcription: the
nucleosome might be transferred from the positively supercoiled DNA in front of the polymerase to
the negatively supercoiled DNA behind it. This idea was tested using a model system in which the
fate of a single nucleosome placed at a defined position on a plasmid was determined after
transcription, and found that the nucleosome moved behind the transcribing polymerase. These
observations were followed up in subsequent work with Dr. Vasily Studitsky, in which evidence was
obtained for a "spooling" model for transcription through the nucleosome. Independently, Dr. Clark
published a paper with a postdoctoral colleague in Dr. Felsenfeld's lab, Dr. Takeshi Kimura,
describing a theoretical analysis of chromatin folding using Manning's polyelectrolyte theory. At the
NIH, Dr. Clark developed a model system to study the events that occur when a gene is activated
for transcription in vivo. The lab purified native plasmid chromatin containing a model gene
expressed at basal or activated levels from yeast cells. Studies revealed that activation correlates
with large scale movements of nucleosomes and remodeling of nucleosomes over the entire gene.
In addition, the lab demonstrated that DNA sequence plays a major role in determining
nucleosome positions in vivo. Most recently, the lab published a genome-wide nucleosome
mapping study using paired-end sequencing, which confirms and extends its observations to the
entire genome. In addition, evidence was presented for perfect positioning of the yeast centromeric
nucleosome, such that the entire centromere is included within the nucleosome on every
chromosome in every cell. The specialized centromeric nucleosome is quite different from
canonical nucleosomes, which are positioned imperfectly, choosing from a range of alternative
positions. The genome-wide approach has worked very well and the lab continues to exploit it
heavily. The other major project in the lab is understanding the cell cycle-dependent regulation of
the yeast histone genes. The lab has shown that the major activator of these genes is the Spt10
protein, which contains a putative histone acetyltransferase domain as well as a sequence-specific
DNA-binding domain.
7.
Section Head
Judy Kassis
Section on Gene Expression
Address
Email: JK14p@nih.gov
Phone: 301-496-7879
Bldg 6B, Rm 3B331,
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Research Interest:
Control of Gene Expression during Development
During development and differentiation, genes either become competent to be expressed or are
stably silenced in an epigenetically heritable manner. This selective activation/repression of genes
leads to the differentiation of tissue types. Recent evidence suggests that modifications of histones
in chromatin contribute substantially to determining whether a gene will be expressed. Our group is
interested in understanding how chromatin-modifying protein complexes are recruited to DNA.
In Drosophila, two groups of genes, the Polycomb group (PcG) and Trithorax group (TrxG),
are important for inheritance of the silenced and active chromatin state, respectively. Regulatory
elements called Polycomb group response elements (PRE) are cis-acting sequences required for
the recruitment of chromatin-modifying PcG protein complexes. TrxG proteins may act through
either the same or overlapping cis-acting sequences. Our group aims to understand how PcG and
TrxG proteins are recruited to DNA. We are also interested in how distantly located transcriptional
enhancer elements are able selectively to activate a promoter that may be tens (or even hundreds)
of kilobases away. Our data suggest that promoter-proximal elements, some of which overlap with
PREs, impart specificity to promoter-enhancer communication. Finally, we are interested in the
coordination between activation by enhancer elements and silencing by PcG proteins. Our data
suggest that certain types of transcriptional activators may be able to overcome the repressive
activity of PcG proteins, which may be particularly important at the PcG target gene engrailed, at
which PcG binding is constitutive; that is, PcG proteins and repressive chromatin structure are
present
even
in
cells
in
which engrailed is
actively
transcribed.
Biography
Dr. Judy Kassis is the head of the Section on Gene Expression, Program in Genomics of
Differentiation, NICHD. Dr. Kassis obtained her Ph.D. in 1983 at the University of Wisconsin,
Madison. She did postdoctoral research at the University of California, San Francisco and then
joined the Center for Biological Research and Evaluation (CBER), FDA as a tenure-track
investigator in 1987. At CBER she conducted research on the control of gene expression and
transposon homing using the model system Drosophila and was a product reviewer and license
chair for biological products. She joined the Laboratory of Molecular Genetics, NICHD as a Senior
Investigator in 1999. Dr. Kassis studies epigenetic silencing by the Polycomb group of
transcriptional repressors using Drosophila as a model system. Her lab was the first to show the
involvement of specific DNA binding proteins in recruitment of Polycomb repressive complexes to
the DNA. She is also interested in how transcriptional enhancers, often located 50kb or more away
from the promoters they regulate, achieve their specificity. She has served on the NIH, NRSA
Genes and Genomics study section since 2002 and is the reviewer of many papers for
Development, Developmental Biology, Molecular and Cellular Biology, and Genetics.
8.
Section Head
Paul Love
Section on Cellular and Developmental
Biology
Address
Bldg 6B, Rm 2B210
Phone: 301-402-4946
Email: LoveP@mail.nih.gov
Research Interest:
Genes and Signals Regulating Mammalian Hematopoiesis
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Our research focuses on the development of the mammalian hematopoietic system. Of particular
interest is the characterization of signal transduction molecules and pathways that regulate T cell
maturation in the thymus. Current projects include the generation of transgenic and conditional
deletion mutants to evaluate the importance of T cell antigen receptor signaling at specific stages
of T cell development. We are also using microarray gene profiling to identify molecules that are
important for thymocyte selection, a process that promotes the survival and development of
functional T cells and the death of auto-reactive T cells. Further, we are analyzing the function of
Themis, a T cell–specific signaling protein newly identified by our laboratory. A recently initiated
area of investigation focuses on hematopoietic stem cells (HSCs). We have begun to characterize
the genes that are important for the generation and maintenance of HSCs and for their
differentiation into specific hematopoietic lineages. These studies have revealed a critical function
for one protein (Ldb1) in controlling the self-renewal/differentiation cell-fate decision in
hematopoietic stem cells.
Biography
Dr. Paul Love earned a B.S. degree in Biochemistry from Syracuse University in 1979 and
received an M.D. and Ph.D. from the University of Rochester in 1987. He completed a residency
program in Laboratory Medicine at Washington University, St. Louis and a fellowship in Human
Genetics in NICHD, before joining the laboratory of Dr. Heiner Westphal (NICHD) as a postdoctoral
research fellow. He became an intramural Principal Investigator in 1993 and is now a tenured
Senior Investigator and head of the Section on Cellular & Developmental Biology in NICHD. The
research focus of Dr. Love’s lab is in the area of mammalian hematopoiesis. The lab has a long
history of studying the process of T cell development, which begins with migration of multipotent
progenitor cells, derived from hematopoietic stem cells in the bone marrow, to the thymus.
Immature T cells then undergo a series of developmental steps in the thymus, including a process
of selection that promotes the development of functional cells and the deletion of overtly selfreactive cells, ultimately leading to the generation of mature “self-tolerant” T lymphocytes that exit
the thymus and populate the peripheral lymphoid organs. Dr. Love’s group has investigated
questions relating to each of these steps in the T cell developmental pathway over the years;
however, the main focus of his lab is the role and importance of signals transduced by the T cell
antigen receptor (TCR) for T cell maturation. Current work includes studies aimed at understanding
how TCR signaling influences susceptibility to autoimmune disease and investigating potential
therapeutic interventions for the treatment of human hematopoietic stem cell malignancies.
9.
Section Head
Todd Macfarlan
Unit on Mammalian Epigenome
Reprogramming
Address
Bldg 6B, Rm 2B211
Phone: 301-496-4448
Email: Todd.Macfarlan@nih.gov
Research Interest:
Exploring the function of histone modifying enzymes during development
A large number of enzymes that post-translationally modify histones/DNA have been identified and
biochemically characterized. A number of these enzymes have also been shown to be essential for
embryo development, mutated in cancers and neurological disease, or important for
transgenerational epigenetic inheritance in model organisms. We are using stem cell based
models of development along with mouse genetics to remove enzymes that post translationally
modify histones and DNA in a tissue specific manner. In particular we are focusing on the time
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period of preimplantation development, where massive reprogramming of the epigenome takes
place, and during formation of the central nervous system, when cells are becoming post-mitotic as
they differentiate into neurons and are thus incapable of replication dependent changes in the
epigenome. With these studies, we hope to gain a further understanding of the importance of
epigenetic information stored in chromatin.
Studying the interplay of transcription factors and chromatin modifying enzymes
Transcription factors have long been known to be the master regulators of cell fate, binding to
specific sequences of DNA and activating or silencing genes that allow specific cell types to carry
out specialized function. More recently, it has been demonstrated that transcription factors can
convert somatic cells into induced pluripotent cells (iPS cells) or from one somatic type to another,
although this process is relatively inefficient. One likely reason this process is so inefficient is that
differentiated cell types carry “restrictive” epigenomes that are less accessible to transcription
factors than the “permissive” epigenomes of embryonic stem cells, which are easily reprogrammed
to somatic cells. We are thus exploring the possibility that chromatin-modifying enzymes gate the
activity of transcription factors during these reprogramming processes (both natural and artificial
reprogramming), and are testing how chromatin-modifying enzymes work in conjunction with
transcription factors to regulate cell fate.
Exploring the regulation and function of endogenous retroviruses
Endogenous retroviruses (ERVs) are the remnants of ancient retroviral infections that have
become a permanent part of the host genome. These sequences make up nearly 10% of
mammalian genomes. It has long been debated whether ERVs and other transposable elements
are nothing more than parasitic elements that have remained in genomes due to their ability to
independently replicate (via retrotransposition) or whether they may provide some selective
advantage to their hosts. One way in which ERVs can influence their hosts is via regulation of host
gene expression. ERVs and other transposons are targeted for silencing by distinct repressive
chromatin generating machinery that can spread to neighboring genes, or can serve as alternate
promoters. We have been studying a particular class of ERVs found in all placental mammals
called ERVLs (MERVLs in the mouse) that very briefly evade silencing in preimplantation
development during zygote genome activation. Morever these ERVL elements appear to serve as
primary or alternate promoters for a large number cellular genes, which has lead us to speculate
that these elements may actually be essential for embryo development. We are interested in two
important questions, 1) How are ERVL elements regulated? and 2) Are ERVL elements critical for
cell
fate
decisions
in
embryo
development?
Biography
Dr. Todd Macfarlan earned his Ph.D. in Cell and Molecular Biology from the University of
Pennsylvania in 2000, where his interest in epigenetic phenomena began while studying the
histone binding and transcriptional repressive activities of THAP domain proteins. After his Ph.D.,
Dr. Macfarlan joined the laboratory of Dr. Samuel Pfaff at the Salk Institute for Biological Studies,
where he continued to study chromatin and epigenome changes during mammalian embryo
development. He was then recruited to the NIH in July of 2012 as part of the Earl Stadtman
Investigator search, in chromosome biology and epigenetics. As a member of the Program in
Genomics of Differentiation, NICHD, Dr. Macfarlan heads the Unit on Mammalian Epigenome
Reprogramming.
10.
Section Head
Richard Maraia
Address
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Section on Molecular and Cell Biology
Bldg 6A, Rm 2A02
Email: MaraiaR@mail.nih.gov
Phone: 301-402-3567
Research Interest:
RNA Metabolism in Cell Biology, Growth, and Development
We are interested in how the biogenesis and metabolism pathways for small RNAs, especially
tRNAs and mRNAs, interact with pathways that control cell proliferation, growth, and development.
We focus on RNA polymerase (Pol) III and the post-transcriptional handling of its transcripts by the
RNA-binding protein La, which, together with La-related protein-4 (LARP4), contributes to
translational control and the cell’s growth capacity. In addition to its major products (tRNAs and 5S
rRNA), Pol III synthesizes other non-coding RNAs. Tumor suppressors and oncogenes mediate
deregulation of Pol III transcript production, contributing to increased capacity for proliferation of
cancer cells. The La protein is a target of autoantibodies prevalent in (and diagnostic of) patients
with Sjögren’s syndrome, systemic lupus, and neonatal lupus. La contains several nucleic acid–
binding motifs as well as several subcellular trafficking signals and associates with non-coding and
messenger RNAs to coordinate activities in the nucleus and cytoplasm. The La protein functions by
protecting its small RNA ligands from exonucleolytic decay. Our recent studies showed that human
LARP4 protects certain mRNAs from decay, in a polyribosome-associated manner. We strive to
understand the structure-function relationship and cell biology of La’s and LARP4’s contribution to
growth and development. We use genetics, cell and structural biology, and biochemistry in model
systems that include yeast, human tissue culture cells, and gene-altered mice.
Biography
Dr. Richard Maraia is a Senior Investigator and Head of the Section on Molecular and Cell Biology
in the Intramural Research Program of the NICHD. Dr. Maraia directs a basic research program in
Molecular Genetics that seeks to understand the influences of genetics, biochemistry, and cell
biology on the programmed metabolism of small nuclear RNAs and messenger RNAs, and how
this contributes to growth and development. Of molecular interest is the structural plasticity of the
human La antigen and related proteins in their ability to accommodate specific binding to a variety
of RNAs that differ in sequence and structure. A major interest is in the biogenesis and metabolism
of transfer RNAs, the genetic adapters that translate the genetic code, and the influences of their
dynamics and relative abundances on codon bias-driven genetic programs involved in normal
growth and in response to the physiologic states of stress and disease. Dr. Maraia received his
B.S. in Biological Sciences from Columbia University and his M.D. from Cornell University Medical
College. He obtained specialty training in Pediatrics at The New York Hospital and in Medical
Genetics at the NIH. Dr. Maraia's service currently includes Chairmanship of the NIH Regional
RNA Club and the International Biennial Conference on RNA Polymerases I & III, and he is
President elect of the La and Related Protein (LARP) Society.
11.
Section Head
Karl Pfeifer
Section on Genomic Imprinting
Address
Email: Kpfeifer@helix.nih.gov
Phone: 301-402-0676
Bldg 6B, Rm 2B206
Research Interest:
Molecular Genetics of an Imprinted Gene Cluster on Mouse Distal Chromosome 7 14 | P a g
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Genomic imprinting is an unusual form of gene regulation by which an allele’s parental origin
restricts allele expression. Imprinting is critical for normal development, and recent studies have
especially emphasized a role for imprinting in normal brain development and function (1). Imprinted
genes are not randomly scattered throughout the chromosome but rather are localized in discrete
clusters. One cluster of imprinted genes is located on the distal end of mouse chromosome 7
(Figure 1). The syntenic region in humans (11p15.5) is highly conserved in gene organization and
expression patterns. Mutations disrupting the normal patterns of imprinting at the human locus are
associated with developmental disorders and many types of tumors. In addition, inherited cardiac
arrhythmia is associated with mutations in the maternal-specific Kcnq1 gene. We use mouse
models to address the molecular basis for allele-specific expression in this distal 7 cluster. We use
imprinting as a tool to understand the fundamental features of epigenetic regulation of gene
expression. We also generate mouse models for the several inherited disorders of humans. We
have generated models to study defects in cardiac repolarization associated with loss
ofKcnq1 function and, more recently, characterized the phenotype associated with loss
of Calsequestrin2 gene function.
Biography
Dr. Karl Pfeifer obtained his Bachelor of Science from the George Washington University,
Washington, DC, in 1978 and his Ph.D. in Biology from the Massachusetts Institute of Technology,
Cambridge, in 1988, under Dr. Lenny Guarente. He joined Dr. Shirley Tilghman at Princeton
University as a Damon Runyon Cancer Research Foundation Fellow for postdoctoral training. He
was recruited by the NIH in 1995.
12.
Section Head
Brant Weinstein
Section on Vertebrate Organogenesis
Address
Email: WeinsteB@mail.nih.gov
Phone: 301-435-5760
Bldg 6B, Rm 3B309
Research Interest:
Organogenesis of the Zebrafish Vasculature
The overall objective of this project is to understand how the elaborate networks of blood and
lymphatic vessels arise during vertebrate embryogenesis. Blood vessels supply every tissue and
organ with oxygen, nutrients, and cellular and humoral factors. Lymphatic vessels drain fluids and
macromolecules from the interstitial spaces of tissues, returning them to the blood circulation, and
play an important role in immune responses. Understanding the formation of blood and lymphatic
vessels is engendering intense clinical interest because of the roles that both types of vessels play
in cancer and ischemia. The zebrafish, a small tropical freshwater fish, possesses a unique
combination of features that make it particularly suitable for studying vessel formation; the fish is a
genetically tractable vertebrate with a physically accessible, optically clear embryo. These features
are highly advantageous for studying vascular development, permitting observation of every vessel
in the living animal and simple, rapid screening for even subtle vascular-specific mutants.
Major aims of the laboratory include developing new tools for studying vascular development in
zebrafish, experimental analysis of vascular morphogenesis, vascular patterning, and lymphatic
development, and forward-genetic analysis of vascular development.
Biography
Dr. Brant M. Weinstein received his Ph. D. from the Massachusetts Institute of Technology and
carried out postdoctoral studies in the laboratory of Dr. Mark Fishman at the Massachusetts
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General Hospital. He joined the NICHD as a Primary Investigator in 1997. He became Deputy
Director of the NICHD Program in Genomics of Differentiation in 2007 and then Director in 2010.
Dr. Weinstein is a leading expert on zebrafish vascular development. His laboratory developed a
widely used confocal micro-angiography method, compiled an atlas of the anatomy of the
developing zebrafish vasculature, developed numerous vascular-specific transgenic fish lines, and
pioneered methods for high resolution in vivo imaging of zebrafish blood vessels. His laboratory
has used all of these tools and methods to make a variety of important discoveries in the areas of
vascular specification, differentiation, and patterning, including a novel pathway specifying arterial
identity, a role for neuronal guidance factors in vascular patterning, a mechanism for vascular tube
formation in vivo, and the identification of a lymphatic vascular system in the zebrafish.
13.
Section Head
Peter Basser
Section on Tissue Biophysics and
Biomimetics
Address
Bldg 13, Rm 3W16
Phone: 301-435-1949
Email: Pjbasser@helix.nih.gov
Research Interest:
Tissue Biophysics and Biomimetics
We attempt to understand fundamental relationships between function and structure in living
tissues, “engineered” tissue constructs, and tissue analogs. Specifically, we are interested in
how microstructure, hierarchical organization, composition, and material properties of tissue affect
its biological function and dysfunction. We investigate biological and physical model systems at
different time and length scales, making physical measurements in tandem with the development
of mathematical and computational models. Primarily, we use water molecules to probe both
equilibrium and dynamic interactions among tissue constituents over a wide range of time and
length scales. To determine the equilibrium osmo-mechanical properties of well-defined
model systems, we vary water content or ionic composition. To probe tissue structure and
dynamics, we employ atomic force microscopy (AFM), small-angle X-ray scattering (SAXS), smallangle neutron scattering (SANS), static light scattering (SLS), dynamic light scattering (DLS), and
nuclear magnetic resonance (NMR) relaxometry. We develop and use mathematical models to
help us understand how observed changes in tissue microstructure and physical properties (e.g.,
mass, charge, and momentum) affect essential transport processes. The most
direct noninvasive in vivo method for characterizing these transport processes in tissues
is magnetic resonance imaging (MRI), which we use to follow microstructural changes in
development, degeneration, aging, and trauma. A goal of our basic tissue sciences research is to
translate our quantitative methodologies and the understanding we glean from them from "bench to
bedside."
Biography
Dr. Peter Basser received his A.B., S.M., and Ph.D. in Engineering Sciences from Harvard
University and then received his postdoctoral training in Bioengineering as a Staff Fellow in the
Biomedical Engineering and Instrumentation Branch (BEIP), NIH. In 1997, Dr. Basser
became Chief of the Section on Tissue Biophysics and Biomimetics (STBB), NICHD and
is currently the Director of the Program on Pediatric Imaging and Tissue Sciences there. Dr.
Basser's group is primarily known for its invention, development, and clinical implementation of MR
diffusion tensor imaging (DTI), and for explaining the physical basis of magnetic stimulation of
nerve fibers. More recently, STBB has been developing several quantitative in vivo MRI methods
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for performing in vivo MRI histology. These include AxCaliber MRI, which measures the axon
diameter distribution within nerve fascicles, and double Pulsed-Field Gradient (dPFG) MRI, which
is used to study distinct microstructural features of both gray and white matter.
14.
Section Head
Amir Gandjbakhche
Section on Analytical and Functional
Biophotonics
Email: Gandjbaa@mail.nih.gov
Address
Bldg 9, Rm 1E116
Phone: 301-435-9235
Research Interest:
Quantitative Biophotonics for Tissue Characterization and Function
Our objectives are to devise quantitative biophotonics methodologies and associated
instrumentations in order to study biological phenomena at different length scales—from
nanoscopy to microscopy—and diffuse biophotonics. We take advantage of our expertise in
stochastic modeling to study complex biological phenomena whose properties are characterized by
elements of randomness in both time and space, such as light-tissue interactions. We explore
various properties of light-matter interactions as sources of optical contrasts, such as polarization
properties, endogenous or exogenous fluorescent labels, absorption (e.g., hemoglobin or
chromophore concentration), and/or scattering. We have used these contrast mechanisms for
tomographic and spectroscopic methods to develop benchtop instrumentation for preclinical and
clinical uses. We are identifying physiological sites where optical techniques might be clinically
practical and offer new diagnostic knowledge and/or less morbidity than existing diagnostic
methods.
Biography
Dr. Amir Gandjbakhche is a Senior Investigator and Head of the Section on Analytical and
Functional Biophotonics of NICHD. He obtained his Ph.D. in physics with a biomedical engineering
specialty from the University of Paris in 1989. He is a Fellow of SPIE, the largest society of optical
engineers. Dr. Gandjbakhche leads a research group that uses different optical sources of contrast
such as endogenous or exogenous fluorescent labels, absorption (e.g., hemoglobin or
chromophore concentration) in order to devise quantitative theories at the board, and designs
instrumentation at the bench, and brings the imaging system to the bedside. Two areas of interest
are the use of near infrared spectroscopy to assess cognitive function in Traumatic Brain Injury and
Autistic Spectrum Disorder patients, and using specific fluorescently labeled HER2 imaging agent
to monitor monoclonal antibody therapy of breast tumor.
15.
Section Head
Joshua Zimmerberg
Section on Membrane and Cellular
Biophysics
Email: ZimmerbJ@mail.nih.gov
Address
Building 10, Room 10D14
Phone: 301-496-6571
Research Interest:
Synaptic Vesicle Isolation and Characterization, Optimization of Receptor Structure, and
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Structure of the Viral Membrane
We study membrane mechanics, intracellular molecules, membranes, viruses, organelles, and
cells in order to understand viral and parasite infection, exocytosis, apoptosis, the mechanism of
immune protection by stem cells and their cytotoxic potential, and immune dysfunction in
microgravity. The overall goals of the exocytosis projects are to understand the mechanisms of
cellular secretion at the physical, biophysical, and chemical levels. This process of protein
secretion is the climax of the secretory pathway and operates in both constitutive and triggered
ways. The process of endocytosis is equally important to retrieve membrane components.
This year, we focused on a purified fraction of exocytotic vesicles, synaptic vesicles. They contain
a variety of proteins and lipids that mediate fusion with the pre-synaptic membrane. Although the
structures of many synaptic vesicle proteins are known, an overall picture of how they are
organized at the vesicle surface is lacking. We developed an improved method for isolating highly
pure and intact squid synaptic vesicles.
In collaboration with Sergey Bezrukov, we discovered that, at lower substrate concentrations,
stronger substrate binding is required and that the deviations from optimal interaction become
more critical as the substrate concentration increases, i.e., higher concentrations require more
precise tuning. Thus, uniporters designed to transport the same molecule in the same cell have to
be optimized with different amino-acid sequences, with one gene coding for a uniporter protein that
functions most efficiently at high solute concentrations, whereas another gene is coding for one
that is most efficient at low concentrations.
Negative staining can provide detailed, two-dimensional images of biological structures while
combining tomography with negative staining can provide three-dimensional images. Basic
requirements for a negative stain for tomography are that the density and atomic number of the
stain are optimal and that the stain is not degraded by the intense electron beam needed to collect
a full set of tomographic images. A commercially available, tungsten-based stain, methylamine
tungstate, appears to satisfy these prerequisites. Tomograms derived from multiple projections of
EM images of the same structure yielded detailed images of single proteins on the surface of
influenza A virus. By comparing these images with published results from other methods, we could
evaluate the negative-stain tomography. Images of surface renderings of the virus are a good fit to
images derived from cryomicroscopy as well as to the shapes of crystallized surface proteins.
Thus, negative stain tomography provides realistic and detailed images of individual molecules in
their normal setting on the surface of influenza A virus.
Biography
Joshua Zimmerberg trained in Developmental Enzymology, General Physiology, Membrane
Biophysics and Neuroscience, and Cell Biology and early Development, with Olga Greengard, Alan
Finkelstein, Adrian Parsegian, David Epel, and Daniel Mazia. He builds teams of researchers to
vigorously pursue the deeper understanding of membrane fusion, fission, phase, hydration,
curvature, and poration as manifested in syncytia formation, cellular secretion, calcium
homeostasis, collagen synthesis, viral infection, fertilization, organelle shape, protein translocation,
channel architecture, toxoplasma entry. Having initiated studies on the long-_term deep tissue and
dynamic single molecule microscopy of living cell membranes, he focuses on pathological
processes in HIV, apoptosis, malaria, sickle cell, insulin resistance, influenza, embryonic stem cell
differentiation, and the effects of microgravity intercellular communications. He is currently
developing new models for the study of pathogenesis in cancer initiation and invasion,
musculodystrophy, lipid droplet formation, viral assembly, and the proteomic imaging of signaling
pathways for developmental control of growth and metastasis. In NICHD, he is the head of the
Program in Physical Biology, the chief of the Section of Membrane and Cellular Biophysics, and
the director of the NASA/NIH Center for Three-_Dimensional Tissue Culture.
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