A. BACKGROUND
1. Genomics and Bioinformatics
Full genome sequencing projects have generated an unprecedented amount of information regarding the
identification and structure of genes from a broad variety of organisms. The anticipated existence of a
comprehensive catalogue of all known human genes together with their nucleotide sequence is intensifying
research efforts on exploration of gene function at the molecular, cellular, organismal and population level.
With the development of new data on gene sequence along with emerging novel technologies, the global
biomedical research enterprise is undergoing a major paradigm shift. This shift is revolutionizing biological
research. Hypothesis-driven science has been the historical modus operandi for the last two hundred years.
However, because of the current exponential increase in the rate genomic data can be collected, a shift to
discovery-driven science is underway. This change will form the basis for genomic medicine that will entail
more intelligent hypothesis generation eventually leading to individual target treatments for many diseases.
Furthermore, preventative medicine will flourish with the identification of an individual’s predisposition to
specific diseases and a much deeper understanding of basic biological phenomena. Therefore, a researchintensive academic center such as UNC-Chapel Hill must integrate its efforts to conduct basic research in all
areas contributing to genome sciences.
The immense quantity of data being generated is just the beginning of this revolution. The next great
challenge is now upon us - to provide meaning to this vast catalog of information, a challenge orders-ofmagnitude more difficult than we have previously faced. Knowing which gene networks and genetic variants
influence disease predisposition and progression in an organism, will contribute significantly to the ability to
develop effective clinical interventions. Thus, the existence of a preeminent basic research program in genetics
and genomics within the context of a major University such as UNC provides the opportunity for bench-tobedside and population-based research. The approaches being applied range from large-scale genome
sequencing to the micro-scale assaying of the metabolic state of a single cell. However, all approaches share the
theme of integrating biology with technology and each requires a need for computational data analysis and
management. It is essential that UNC develop the capacity to be a leader in establishing as well as maximizing
the use of these emerging technologies. The application of the tools of genomics will have a profound impact on
scientific discovery, the delivery of health care, our legal system and on many aspects of our culture and
society. As a result, these technologies and their scientific uses demand integration with the ethical, legal, social
and technology transfer programs on campus.
Techniques for the exploration of large datasets are a recent complement to the hypothesis driven,
experimental approach of classical biology. In data mining, the fields of statistics, machine learning, and
pattern recognition are applied in a systematic way to large datasets in order to synthesize novel ideas and
generate hypotheses for further study. Related to this are visualization techniques for complex highdimensional datasets. Such data exploration techniques are being applied especially to the case record and
population databases used by clinical researchers and epidemiologists, and to bibliographic databases.
The field of genomics involves a variety of technologies that present difficult computational and
statistical challenges. There are unsolved problems in genomic sequencing and assembly, the analysis of
expressed sequence tag data, multiple sequence alignment, analysis of nucleotide substitutions, inferring
phylogenetic history, pattern recognition in nucleic acid sequences (i.e., the annotation of genes), nucleic acid
secondary structure, the analysis of expression data, the identification of polymorphisms, the construction of
genetic and physical maps, and the dissection of the genetic basis for complex traits, to name a few.
Proteomics presents its own set of challenges, such as the identification of individual proteins or sets of
proteins from NMR and MS profiles, inferring protein structure from crystallographic data, predicting structure
from primary sequence or by homology modeling, predicting function from sequence, structure or evolutionary
information, and the identification of post-translational modification motifs.
An understanding of the workings of the cell necessitates an appreciation for the properties of
biochemical networks, signalling cascades, and the interactions between external and internal cellular stimuli.
On the experimental side, the field of metabolomics attempts to extract some of this information by
accumulating large datasets on the varying abundance of metabolites in the cell. On the more theoretical side,
physicists and mathematicians attempt to apply more generic models of complex systems to understand cellular
dynamics. The union of these two approaches will come through the application of biological datasets to the
construction, parameterization and validation of such models as we approach a complete catalogue of all the
interacting parts in the cell. The future will also likely call for more systematic and data-intensive approaches
to understanding development and differentiation among cells.
2. Demand for specialists in bioinformatics.
There is a tremendous demand for biomedical informaticists who have the skills to address basic
problems in all areas discussed above. It is anticipated that the need for biomedical informaticist will grow over
the next few decades. Charles DeLisi of Boston University predicted "biology will eventually become the most
computational science, surpassing physics" (cited in Wallace 20011). "Unfortunately", a recent National
Research Council workshop report on bioinformatics (Pool and Esnayra, 2000) notes, "supply does not seem to
be keeping up with demand". The report cites several reasons. There is competing demand for people skilled
with computers in many areas of the private sector. Since biomedical researchers are generally underpaid
relative to other areas, it has been difficult to attract them to academic departments. The January 1st 2000 issue
of Chemical & Engineering News [79: 47-55 (2001)] had a feature article entitled “The Hottest Job in Town”
with a subheading, “Opportunities abound in bioinformatics but qualified candidates are hard to find.” This
article lays out the basis for the recent growth of bioinformatics and notes that the educational opportunities in
the field have simply not kept pace with the burgeoning demand for trained individuals. It also pointed out that
this situation is not static and listed 16 programs in bioinformatics and computational biology that came from a
search of the World Wide Web.
Another reason for the deficit of qualified people in biomedical informatics is the need to be conversant
with multiple, and very different, disciplines. Disciplines as diverse as computer science, genetics, clinical
medicine, structural biology, biophysics, and biochemistry all are integral to biomedical informatics. Given the
complexity of the technologies being employed in all these fields, it is a serious challenge for an academic
training program to produce a competent graduate in a finite amount of time. According to NRC Workshop
participant Gio Wiederhold (quoted in Pool and Esnayra, 20002), "We can't expect every student interested in
bioinformatics to satisfy all the requirements of a computer science and a biology degree. We have to find new
programs that provide adequate training without making the load too high for the participants".
The development of graduate programs in both bioinformatics and genome technology is central to the
broader genomics enterprises at UNC. It is also clear that the development of a vigorous graduate program in
biomedical informatics will depend on effective interaction and collaboration among the relevant scientists,
including biologists and clinicians, faculty interested in the computational and informatics aspects of biology,
and engineers interested in applications related to genome technology. With this in mind, the proposed program
is structured to benefit from diverse faculty interests and priorities, while anticipating rapid change in the next
few years as the field of biomedical informatics evolves.
3. UNC-Chapel Hill is prepared to launch a Predoctoral Training Program in Bioinformatics and
Computational Biology.
According to the working definition used by the National Institutes of Health, Bioinformatics is defined
as the "research, development or application of computational tools and approaches for expanding the use of
biological, medical, behavioral or health data, including those to acquire, store, organize, archive, analyze or
visualize such data" (http://grants2.nih.gov/grants/bistic/CompuBioDef.pdf). The same document defines
Computational Biology as “The development and application of data-analytical and theoretical methods,
mathematical modeling and computational simulation techniques to the study of biological, behavioral, and
social systems”. The success of the genome science initiative at the UNC-CH will depend on the presence of a
1
Wallace, R. Bioinformatics: key to 21st century biology.
BioMedNet, Issue 99, March 30, 2001.
http://news.bmn.com/friend/b63302bd70/%2Fhmsbeagle%2F99%2Fnotes%2Fadapt
Pool, R. and J. Esnayra (2000) Bioinformatics: Converting Data to Knowledge. National Academy Press.
Washington, D.C.
2
strong bioinformatics program at all levels, from education and training to support and research. Since the
fields of genomics and proteomics also present a wide variety of important analytical problems that are of great
value to basic research in the mathematical, computational and statistical sciences, there is overwhelming
enthusiasm for a new Training Program in Bioinformatics and Computational Biology (BCB) among a wide
spectrum of UNC-CH academic and research units (see Appendix 1, which includes letters of support from
UNC-CH Vice-Chancellor for Research and Graduate Studies Tony Waldrop, Director of Carolina Center for
Genome Science Terry Magnuson, Director of the Office of Information Technology Judd Knott, and letters of
support from 18 Chairs of basic science Departments and Schools). Furthermore, as a result of a competitive
proposal submitted recently by a core group of 15 UNC faculty working in the areas of bioinformatics and
computational biology to the UNC Office of the President, a seed funding in the amount of $150,000 per year
for three years has been obtain from UNC. This funding allows starting the training program as soon as in the
Fall of 2002, and an Admission committee will begin considering applications from entering first year and
existing second year students in the end of May. However, additional support that can be provided as a result of
this grant application from NIH is vital to develop and sustain the BCB training program further.
It is generally recognized that the most effective and productive way to foster synergies among different
disciplines is through shared graduate training. Both within the United States and globally, educational
opportunities in the field of bioinformatics have not kept pace with the burgeoning demand for trained
individuals in both academia and industry. The need for bioinformatics professionals is particularly acute in
North Carolina where biotechnology is a major component of the state economy. Thus, by offering BCB,
UNC-CH serves an institutional need as well as providing a concrete benefit to the state. This program will also
serve students well, as bioinformatics trainees have excellent career prospects for the foreseeable future. Such
prospects are indicated by obvious interest from major local pharmaceutical and biotech companies (see letters
of matching support from GlaxoSmithKline and BD Biosciences which agreed to provide one additional
graduate positions each for every year of the BCB program as a matching support for the proposal funded by
UNC Office of the President).
Developing a rigorous graduate training program in bioinformatics presents special challenges. A
bioinformaticist works at the intersection of multiple different disciplines, including but not limited to
biochemistry, biophysics, computer science, genetics, information science, statistics and structural biology. In
order to produce a competent graduate in a finite amount of time, it is necessary to develop a curriculum that
truly cuts across academic disciplines, rather than being a sum of multiple independent degrees. In addition,
students come to bioinformatics from very different backgrounds (e.g. recent computer science undergraduates
with little exposure to biology and biology undergraduates with little exposure to computer science). Only a
flexible program at an institution with a wide variety of offerings can accommodate such a diversity of student
backgrounds. UNC-CH is well equipped to deal with both of these challenges, and the proposed Bioinformatics
and Computational Biology Training (BCB) program is designed to address them.
The BCB Training program at the University of North Carolina will provide a unique training
experience for talented graduate students. The training faculty are committed to providing a fertile, yet
challenging program that will foster creativity and open discourse among students and faculty. We are
committed to the power of diverse approaches, not only from the technical side, but also from the perspective of
the diverse thought processes that these disciplines demands. Modern BCB trainees must be fearless in their
ability to evaluate, embrace, and employ new technologies when appropriate in their careers. They will receive
this training in BCB at UNC-CH.
Our strategy will begin with recruitment of the top first-year students entering the various biomedical
graduate programs at UNC-Chapel Hill. The individual departments and interdisciplinary programs at UNC-CH
recruit students to their respective programs. The BCB training program will identify elite students enrolled at
UNC and encourage them to enter the training program. An Admissions committee will select students on the
basis of the student’s academic record, research experience and interest in the BCB programmatic goals.
Students will be introduced to the faculty at a BCB retreat held in the beginning of fall semester, as well as in
the various activities sponsored by individual departments. The selection of enrolled students for the training
program will allow us to focus on building a unique training environment rather than recruitment. Our goal will
be to enroll 8-10 students per year in the BCB training program, of whom six will be supported by the training
grant.
This training initiative will provide students ready access to BCB faculty across campus interested in
developing methods, approaches and applications to tackle complex biological problems. Many core faculty
mentors (TABLE) specializing in biocomputing and bioinformatics collaborate with various experimental
resource faculty (TABLE) who provide challenging and experimentally significant problems and generate
experimental data used by the core faculty to develop their empirical models. Students will sample a variety of
research laboratories, both computational and experimental in their first and a half years in a series of up to
three semester-long laboratory rotations. The Executive committee will ensure that each student is exposed to
different questions, approaches or technologies in their rotations. The BCB curriculum includes training in
research, teaching and presentation. To accomplish this goal, we have developed new courses and provide an
infrastructure of faculty and student mentorship to support laboratory training and intellectual development of
BCB students. BCB is a discipline that integrates several experimental, theoretical, and computational
disciplines, combining new developments in the laboratory with new developments in information technology.
Any effort to expand in this area faces the challenge of successfully integrating the separate disciplines that
interact to make BCB so powerful. The BCB will be a program where different disciplines are brought together,
resources shared, and interdisciplinary communication encouraged.
Students are free to choose a particular laboratory (or two laboratories with shared interests as
appropriate) to carry out their thesis research. As students proceed in their career at UNC-Chapel Hill they will
have opportunities to present their research in laboratory group meetings. To formalize the oral presentation
aspect of their training, third year students (and beyond) will present their research to first and second year
CMB students in a joint seminar; although the support is requested only for two years for each student, we
emphasize the community building aspect of the training program and wil request that all trainees continue to
participate in programmatic activities such as seminars and symposia at least until the graduate from their
respective departments. In addition, several of the senior students will comprise a panel to evaluate their peer’s
presentation. This student-led seminar serves a variety of important functions. The seminar provides an in-depth
portrait of the research being carried out in individual laboratories. First-year students will be able to use these
seminars to help in making their decision on laboratory rotations. Since first-year students will hear
presentations by the senior students, faculty have an added incentive to ensure BCB students in their laboratory
are well trained. Secondly, the seminar provides speaking opportunities for senior students, and thirdly, the
graduate student evaluation panel provides feedback to the student in the absence of the faculty advisor.
Students get exposure to the peer-review process in a non-threatening environment, yet simultaneously are
provided with critical comments regarding their presentation skills and scientific research.
The ability to bring faculty with interests in bioinformatics and computational biology in a training
program that strives to expose students to a variety of systems and approaches should be realized at UNCChapel Hill. The BCB training faculty is committed to creating a training environment that will provide the
multitude of skills required for information-rich science in the new millennium. This task has changed with the
changing landscape of science. We welcome the challenge to train the next generation of scientists and teachers.
Depending on the specific content of their research, this training program will produce specialists in
bioinformatics and computational biology, who will be able to enter and successfully compete in the job market
at the end of the training period. Broadly speaking, any training program can produce two types of researchers:
those that satisfy the demand (a strong program) and those who create the demand (an outstanding program).
We certainly believe that this training program will continue to evolve to produce a growing number of
researchers whose qualifications will allow regarding our program as outstanding.
4. INSTITUTIONAL BACKGROUND, HISTORY, AND COMMITMENT TO THE BCB
TRAINING PROGRAM
a. History of genomics and bioinformatics at UNC-Chapel Hill. [JEFF: PLEASE LET ME
KNOW YOUR SUGGESTIONS/CORRECTIONS HERE)
In 1998, recognizing the growing importance of the experimental and computational genomics research,
the then Vice-Chacellor for Research Dr. Tom Meyer commissioned two task forces, in genomics and
bioinformatics, to assess the needs of UNC campus in developing these disciplines. The genomics task force
included Associate Dean of the School of Medicine Dr. Bill Marzluff and faculty members Drs. Jeff Dangl,
Rosann Farber, Susan Lord, and Clyde Hutchison. The Bioinformatics task force included Drs. Sharon
Campbell, Tom O'Connell, Iosif Vaisman, David Fenstermacher, Brenda Temple. In January 1999, these
task forces produced a joint White Paper addressed to senior UNC administrators. In this document, the task
forces proposed an Initiative in Genome Science to establish intellectual leadership in the fields of functional
genomics and bioinformatics. The major components of this initiative were to initiate new faculty appointments,
expand research efforts and research facilities, develop a computational infrastructure, and establish an
education program in experimental and computational Genome Science at all levels.
Realizing that the maximum benefits of the genomics revolution is best achieved in an environment that
fosters free communication and collaboration amongst investigators with complementary skills, the
administration of this university moved quickly in response to the White letter. Fortunately, UNC-Chapel Hill
has been known for fostering interdisciplinary interactions, and strength in several of the key areas of
genetics/genomics already existed on campus. Thus, UNC has recruited a noted mouse geneticist, Dr. Terry R.
Magnuson from Case Western Reserve University to establish both the Carolina Center for Genome
Sciences (CCGS) and the new Department of Genetics. 18 faculty positions have been allocated to the CCGS.
In addition, nine positions in Bioinformatics and Computational Biology have been created between UNC
School of Medicine and College of Arts and Sciences in order to recruit predominantly young specialists
representing various aspects of these disciplines. CCGS was formally approved by the UNC Chancellor on
August 11, 2001, and the following goals of CCGS have been defined to translate genetic/genomic advances
into cutting edge science, to advance the practical application of medicine and to define social, legal and
business policies as we look to the future.
 provide leadership in studying biological sciences in the context of whole genomes
 explore the relationship between genomic organization and biological function and
malfunctioning of genes as well as interacting networks of genes
 explore the relationships between the genomic organization and the disease state
 explore the relationship between genomic organization and the evolutionary process
 apply genetic and genomic approaches and techniques to solve specific biological problems
 investigate the interactions between genomes and the environment
 establish goals relating to genome output –proteomics- and pharmacogenomics
 become a leader in establishing public policy by providing a focus for the larger campus
community on genetic and genome-related issues, which includes medical, ethical, legal and
corporate issues
 develop training opportunities in genomics at the undergraduate, pre-, postdoctoral and
graduate medical education level
 support technology-based research into tools for deciphering genome function and for
translation into medical practice
 develop experimental, theoretical, and computational research tools to enhance genomic
research
 organize and maintain core facilities that provide the latest technologies essential for
genetics/genomics-related research
 promote the distribution of novel genomic technologies through technology transfer
UNC-CH has committed substantial resources (Appendix 2) to establishing CCGS as a University-wide
Center, reporting directly to the Dean, School of Medicine/Vice Chancellor for Medical Affairs. The CCGS
focuses on genomics as an integrated academic discipline on campus, stimulated by projects related to the
subject area. There are six scientific disciplines that have contributed to the genome era and will continue to
contribute to the post-genome era of function and these include biology, chemistry, mathematics, physics,
computer science and engineering. The CCGS vision plan integrates these disciplines into two umbrella
programs: experimental genomics (hypothesis driven research) and analytical genomics (discovery driven
research using computational research tools). In addition, a social genomics program will be developed to focus
on policy driven research in the areas of ethical, legal and business ramifications of managing individual
genomic data. Finally, all three of these areas will have a major impact on training the next generation of
students from the undergraduate to the postgraduate level. As a result, education was defined as a fourth
component of the CCGS.
The important goal of the CCGS is to develop a natural synergy in the form of mutual input-output
relationships between these four focus areas. For example, analytical genomics relies on data provided by the
experimental researcher. In return, analytical models help experimental scientists to focus hypotheses. The
combined output from these will have major ramifications on molding public policy issues in the coming
decades, which in turn will reveal additional areas requiring further experimentation. Likewise, the need for
skilled genome scientists, medical care personnel capable of integrating genome discoveries into patient care,
and policy experts knowledgeable of the benefits of genome science to mankind will require integration and
free information flow between all units of the CCGS. The CCGS would promote its mission through a
combination of intellectual, educational and service activities. This will be achieved by coordinating faculty
recruitment and program development amongst the College of Arts and Sciences, the School of Information and
Library Sciences (SILS) and the five Health Affairs Schools: Medicine, Public Health, Pharmacy, Dentistry and
Nursing. The close working relationship between the College, SILS and the Health Affairs Schools uniquely
positions UNC-Chapel Hill to assume a leadership role in the application of genome sciences and health
outcomes. This creates an exciting paradigm for bench-to-bedside-to-population-based research.
One of the first activities of the new Center was to organize a Research Triangle Park wide retreat and
bioinformatics curriculum development workshop, which took place on May 11, 2001. More than 70 UNC
faculty including high level academic administrators were present, as well as representatives from industry in
the RTP. Disciplines and departments represented included Medicine, Pharmacy, Epidemiology, Statistics and
Biostatistics, Biology, Microbiology and Immunology, Genetics, Information and Library Science, Computer
Science, Biomedical Engineering, Mathematics, and Operations Research. The discussions between
participating faculty at that retreat as well as in the following months stimulated the development of the current
proposal as well as helped establishing a faculty recruitment strategy.
The discussions at the retreat on May 11 emphasized that recent advances in various high-throughput
technologies (combinatorial chemistry, high-throughput screening, genomics, proteomics, etc.) prompt to reevaluate and expand the content and scope of training of new generations of scientists in the fields of
bioinformatics and computational biology. Taking into account campus-wide interests, research and
educational strengths and the support of the faculty and administration, we believe that the expanded training
program should provide students with diverse backgrounds (e.g., primarily computational or mathematical, or
primarily biological or chemical) to obtain a uniform and in-depth training in a singly program structured
around several common core courses. The training program will provide support for predoctoral students (for
two years) who will join the program most of the time in their first year, although we will be also conbsidering
applicants who have completed one year of studies in respective PhD programs. The proposed BCB training
program will operate under the auspices of CCGS and will focus on the professional development of trainees as
discussed in the Program Plan section..
b. Biomedical Research and Training at the University of North Carolina at Chapel Hill.
The University of North Carolina at Chapel Hill has a broad spectrum of biomedical research involving
over 180 laboratories in the School of Medicine, College of Arts and Sciences and School of Public Health.
Currently we are 14th in overall NIH funding, and both our funding and national ranking have been steadily
improving over the past decade. Characteristic of the research environment at UNC-CH is the strong
collaborative environment that routinely brings together research programs from several different departments
in interdisciplinary research efforts. Particular areas of broad strength at UNC-CH include: development of
mouse models of disease; signal transduction mechanisms, particularly G-protein signaling, integrin based
signaling and growth factors; fundamental mechanisms in cell cycle regulation and mitosis; development and
genetic studies of model organisms, including yeast, Drosophila, Arabidopsis and C. elegans; mechanisms of
chromosome segregation, DNA repair and recombination; biophysics and structural biology. In addition, there
are formal interdisciplinary research programs involving groups of investigators, clinical and basic scientists,
working on fundamental biology of important diseases. These include the Cystic Fibrosis Center, studying the
fundamental biology of lung epithelium; the Gene Therapy Center, developing new vectors for gene delivery;
and the Lineberger Comprehensive Cancer Center, integrating study of basic mechanisms of cell growth with
specific human tumor models.
An important component of the Biomedical Research Program at UNC-CH is the training of young
scientists. There are eleven Ph.D. programs in the biomedical sciences, eight of which are directed by
Departments, including 7 in the School of Medicine (Biochemistry and Biophysics, Cell and Developmental
Biology, Cell and Molecular Physiology, Pathology and Laboratory Medicine, Pharmacology, Biomedical
Engineering, Microbiology and Immunology), the Department of Biology in the College of Arts and Sciences,
and three campus-wide Curricula that grant Ph.D. degrees (Genetics and Molecular Biology, Neurobiology and
Toxicology). Together these programs enroll about 75 new students each year and there is a steady-state level
of over 300 graduate students being trained in biomedical research.
There has also been a dramatic expansion of organized interdisciplinary training efforts at UNC-CH in
the past four years. The examples of Institutional training programs organized similarly to the proposed BCB
program include Medical Informatics Training Program (currently directed by Dr. Tropsha; the program is
currently in its tenth, and last, year of existence), Cell and Molecular Biology Training Program funded five
years ago, Cellular and Molecular Biophysics program (funded by an NIH training grant), Cancer Biology
(funded by an NCI training grant), and training in functional genomics of model organisms (funded by Novartis
to the Department of Biology in 2000). All of these programs offer interdisciplinary training with the students
receiving their Ph.D.’s in one of the existing Ph.D. programs. The M.D.-Ph.D. program has been expanded and
more formally structured. The School of Medicine made a major financial commitment to this program and
under the leadership of Dr. Gene Orringer starting in 1997; the M.D.-Ph.D. program has flourished and recently
(July, 1999) received an MSTP grant from NIH. These students may receive their degrees from any of the
Ph.D. programs and the first students have entered their graduate programs in the last two years (after
completing two years of Medical School) and have enhanced the graduate programs significantly. In fact, two
members of the MD/PhD program, Dan Herman and Brad Powell, have been funded by the Medical informatics
training grant directed by Dr. Tropsha.
Two of these programs play a specific role in the context of the proposed BCB program. The
Biophysics program is discussed below in the context of joint training of some students in both molecular
biophysics and BCB. A new mechanism for recruitment and admission of students interested in careers in
biomedical research, the Interdisciplinary Program in Biomedical Sciences (IBMS), has been established
several years ago. The IBMS program was initiated by the chairs of the Basic Science Departments and
Department of Biology, with the enthusiastic support of the Dean of the Medical School. The IBMS program
provides flexibility in graduate student recruitment. The IBMS students (currently 12-16/yr with plans to
increase up to 20-25/yr with the new Genome Sciences Center and expanded faculty in the Cancer Center) enter
into their first year of graduate school with the option of working with any of the approximately 180 faculty in
the Biomedical Research programs. After a first-year of coursework and research rotations, they then choose a
thesis advisor and select the Ph.D. program from which they will receive their degree. The IBMS program is
administered by the Program in Molecular Biology and Biotechnology and is directed by Dr. Sharon Milgram.
The department chairs meet regularly to discuss graduate training programs, both to discuss course
offerings as well as the IBMS program. The collegiality among the Chairs and Curriculum Directors has been
essential for the successful development of the wide variety of training opportunities for students at UNC-CH.
One consequence of this has been an agreement on uniform stipends for students in the various Basic Science
Departments. Each year the department chairs and curriculum directors meet to set the stipend, currently
$18,000 for 2001-2002, and $18,500 for 2002-2003.
The availability of the IBMS program has expanded the pool of students applying for graduate school at
UNC-CH. These students are typically applying to several broad-based programs at a number of institutions,
but not to individual departmental programs. The IBMS program provides a unique opportunity to recruit “nontraditional” students with very strong prior background in one of the disciplines relevant to BCB (e.g., genetics
or, on the contrary, computer science) but insufficient background to join one of the departmental PhD
programs. For instance, we are currently considering an application to the BCB program for an individual with
years of industrial programming experience and practical knowledge of biochemistry who would like to obtain
PhD in one of biomedical disciplines with the emphasis in bioinformatics. This person can be admitted via
IBMS program, supported by the BCB program, and concentrate in his first year on both taking core BCB
classes as well as remedial classes to prepare himself for a biologically oriented PhD granting curriculum. Thus
a returning student applying to graduate school who identifies the BCB as a program of interest to them will
likely apply to IBMS.
c. Core Facility Infrastructure.
The University of North Carolina is committed to making important core research technologies
accessible to our students and faculty. The Core Facilities will be an integral component of the BCB training
program. The core facilities are coordinated by the Research Advisory Committee in The School of Medicine,
which monitors the effectiveness of individual core facilities and also makes recommendations regarding the
investment of new resources. The philosophy behind every core facility is to make state-of-the-art technology
accessible to our researchers on a cost-effective, first-come/first-served basis. Many core facilities have
substantial core funding from extramural core grants, the UNC Program in Molecular Biology and
Biotechnology or individual departments or centers, with recharge mechanisms recovering facility costs not
borne by other sources. Often there is support for the core director’s salary, with recharge revenues covering
the costs of supplies and technical support. Each of the core facilities is directed by a skilled professional
(usually a Ph.D.) who is not a tenure-track faculty member, and whose primary responsibility is to manage the
core. These facility directors are a critical resource; they routinely train students and fellows in the relevant
principles and methodologies, attend appropriate scientific meetings, and engage in collaborative research with
faculty. UNC-CH currently has a relatively large number of long-standing, highly successful core facilities
(visit these cores at www.med.unc.edu/corefacilities.htm). Some that are relevant to this application since they
support the work of either core faculty or resource faculty deserve special mention; these are:
UNC Center for Bioinformatics & the Structural Bioinformatics Core. These two facilities are closely
linked, thematically and operationally. Both have as their primary mission, promoting the use of computational
tools to process the immense flood of new information generated by genomics and proteomics. Dr.
Fenstermacher, director of the Center for Bioinformatics, routinely holds workshops to instruct students in
DNA, RNA and protein sequence analysis, database-mining strategies, and molecular modeling, and he also
regularly assists investigators (particularly graduate students) with specific research problems. The Structural
Bioinformatics Core, which is directed by Dr. Brenda Temple, offers a variety of molecular graphics-based
services including sequences alignment, domain analysis, structure predictions, and molecular dynamics. It also
offers specialized services pertaining to crystallography (e.g., data reduction, molecular replacement, structure
refinement) and NMR (spectral analysis, model building and refinement). Dr. Temple teaches these
methodologies to graduate students in both formal and informal classes. Additionally, Drs. Fenstermacher and
Temple serve as liaisons to the central computing facility at UNC-CH, and are responsible for maintaining a
large set of program licenses that are available to all UNC investigators.
Proteomics & Mass Spectrometry Core. This core was developed during the past several years to assist
UNC-CH investigators in identifying proteins, characterizing protein modifications, and measuring differential
protein expression. Dr. Christoph Borchers, an experienced protein mass spectroscopist, was recruited to
Biochemistry and Biophysics in March, 2001 and serves as the faculty advisor. Directed by Dr. Marshall Pope
and funded with a large gift to the School of Medicine the facility includes a MALDI/TOF/TOF for use in
identifying proteins from in-gel proteolytic digests, a Quadruple/Time of Flight (Q-TOF) for sequence analyses
and high sensitivity LC/MS/MS experiments to characterize modified proteins and peptides, and a Reflex III
MALDI/TOF with reflection and delayed extraction electronics. Additionally, a triple quadruple (3Q) MS with
a binary HPLC system for peptide and small molecule separations, and an ABI Procise 494 sequencer for Nterminal sequencing of purified peptides and proteins (~1 pM level) are also present. For data acquisition,
handling and processing, a LAN infrastructure, comprehensive Oracle-based LIMS system, protein databases,
as well as sophisticated and customized software programs for sample tracking and database searching are
being integrated into a multi-processor server provided and supported by the UNC Center for Bioinformatics.
The facility has identified >150 proteins since March, mapped 5 novel phosphorylation sites on different
proteins, and contributed to the funding of nearly a dozen new grants.
Gene Array Core. This facility is under the joint direction of Dr. Charles Perou, who as a Fellow with
Pat Brown at Stanford was responsible for the initial application of gene array technology to studies of human
breast cancer, and Dr. David Threadgill, a mouse geneticist and one of several investigators who first knocked
out the EGF receptor gene. The facility, which is partly funded by a new HHMI grant, as well as several
external grants, contains a Genome Systems Microarrayer for printing chips containing up to 12,000 genes per
slide, an Affymetrix reader for analysis of commercial oligonucleotide-based arrays, and an Axion scanner for
data analysis. With this instrumentation, the facility can make and analyze microarrays for measuring the
expression (i.e., mRNA levels) for large numbers of genes simultaneously. Initially, the focus is on performing
analyses for yeast, Drosophila, Arabidopsis, mouse and human; the facility is now preparing DNAs for the
6000 yeast ORFs as well as for 40,000 human genes. Necessary computer support for data analysis is also
provided through the Bioinformatics Center.
d. Support for graduate education at UNC-CH.
Extensive support for graduate education is provided by the University of North Carolina at
Chapel Hill. Within the Medical School, each of the Basic Science Departments provides substantial resources
for support of graduate programs within their departments and to the Interdisciplinary Program in Biomedical
Sciences. This amounts to about $160,000 per year toward graduate education for each of the six departments.
These funds are used for supporting students during their first year and for graduate student recruitment. In
addition the major research centers (Cancer Center, Neurosciences Center, Genome Sciences Center and
Program in Molecular Biology and Biotechnology) provide substantial support for graduate students who work
within those various centers, amounting to about $100,000/year to the IBMS program. The Dean of the
Medical School provides approximately $120,000/yr in support for the IBMS program, and approximately
$150,000 in support each to the Genetics and Molecular Biology Curriculum, the Neurobiology Curriculum and
the Toxicology Curriculum, from which students in the Cell and Molecular Biology Training program may
receive their degrees. The Dean also provides about $500,000/yr toward support for the M.D.-Ph.D. program.
The PMBB provides administrative support for the IBMS program. The College of Arts and Sciences provides
supports for graduate students largely in the form of teaching assistantships. In the Department of Biology, the
first-year graduate students (about 7-10/yr in Cell, Molecular and Developmental Biology) are supported by
teaching assistantships. In addition the Department of Biology provides funds for recruitment of these students.
The Graduate School has several graduate fellowship programs and in recent year a number of fellowships have
been awarded to students working in Cell and Molecular Biology.
Changes in Graduate Training at UNC-CH. During the last five years significant changes have
occurred in graduate training at UNC-CH under the leadership of Dr. Linda Dykstra, Dean of the Graduate
School. A health insurance program for all graduate students has been instituted. The program was initially
funded by the University, and now is funded according to the funding source paying the student (funded by the
University for students paid from state funds, and funded by research grants or training grants for students
supported on these grants). The state of North Carolina had made available tuition remission for out-of-state
students for the out-of-state portion of tuition for many years. However, there were insufficient funds to cover
all the eligible students and students were still responsible for the in-state portion of tuition. Under the
leadership of Drs. Linda Dykstra and Tom Meyer, then Vice-Chancellor for Research, additional funds have
been obtained from the legislature for out-of-state-tuition as well as funding for in-state tuition for the first time.
As a result of these new resources committed by the state every student in the biomedical sciences programs
receives both in-state and out-of-state tuition remission for five years. Since the NIH training grants no longer
provide full tuition coverage for trainees, the Dean of the Graduate School gives first priority for tuition
remission to students supported by training grants. Dr. Marzluff, in his role as Associate Dean for Research in
the School of Medicine, is responsible for allotment of tuition remission within the School of Medicine.
The health insurance program and the increased tuition remission are two examples of the progress
made by the Graduate School in improving the university support for graduate training. Dr. Dykstra, Dean of
the Graduate School, is a major asset to UNC-CH and has been an extremely successful advocate for the
enhancement of the graduate programs at UNC-CH.
In summary, the recent UNC investment in developing research and information
technology infrastructure for genomics and bioinformatics, aggressive recruitment efforts in
these disciplines, and seed grant obtained from the UNC Office of the President, this institution
is positioned extremely well to initiate a much needed BCB training program. The content of
the Program is discussed in the next section.