The Nebraska Center for Rapid
Bioanalysis
An Overview of the NIH COBRE Program
David S. Hage
COBRE Retreat - January 16, 2009
Overview of Presentation
 An
Introduction to the NIH COBRE
Program
 Rationale
for a COBRE Proposal in Rapid
Bioanalysis
 Details
behind the COBRE Proposal to
create a Center for Rapid Bioanalysis
What is the NIH COBRE Program?
(Centers of Biomedical Research Excellence)
Program Objectives:
 To strengthen an institution’s biomedical
research infrastructure through the
establishment of a thematic multidisciplinary center
 To
enhance the ability of investigator’s to
compete independently for complementary
NIH individual research grants
Details of the NIH COBRE Program

Program supports initiation and development of unique,
state-of-the-art biomedical and behavior research in the full
spectrum of basic and clinical sciences

Application must have a thematic focus

COBRE awards are supported through the IDeA Program,
aimed at states with historically low aggregate success
rates for grants from NIH

A substantial commitment on the part of the institution is
required to provide additional faculty lines in the thematic
area

Awards are made for 5 years, renewable, with up to 1.5
million (direct costs) being awarded per year; an additional
500 K may be requested in year 1 for facility renovations
Structure of a COBRE Grant

Description of PI


Qualifications – Background, Funding History,
Mentoring, etc.
Overall Research
• Descriptions of 3-5 projects to be performed by junior
faculty

Administrative Core
• Organization, plans for development of Center and junior
faculty

Research Core Facilities

Alteration & Renovation (if applicable)
Rationale for Creation of Nebraska Center
for Rapid Bioanalysis

Many areas of research in biotechnology,
medical research and pharmaceutical science
are turning to more rapid screening or analysis
methods

Examples include:
Proteomics
Glycomics
Metabolomics
DNA Sequencing
High-throughput Screening of Drugs
Identification & Analysis of Biomarkers
Clinical Assays
Combinatorial Chemistry
Rationale for Creation of Nebraska Center
for Rapid Bioanalysis (Cont’d)

Need for improved and more rapid bioanalytical
methods is recognized in several parts of NIH
Roadmap for Medical Research




Building Blocks, Biological Pathways, and Networks
Molecular Libraries and Imaging
Human Microbiome Project
Among the more than 70 COBRE programs in
existence, none deals primarily with bioanalysis
Current Research Interests/Strengths at
UNL & UNMC in Rapid Bioanalysis

Mass Spectrometry
Rapid PCR/DNA Sequencing

NMR
Microfluidics/Nanofabrication

Chemical Separations
Combinatorial Chemistry

Electrochemistry
Single Molecule Imaging &
Manipulation

Optical Spectroscopy
o
Although instrumentation and facilities are available in
these areas, UNL and UNMC currently lack a critical
mass of researchers and the infrastructure needed to
achieve national leadership in bioanalysis
Complementary Nature of Center for Rapid
Bioanalysis with Other COBRE
Programs/Efforts in Nebraska

Center for Virology (UNL)

Center for Redox Biology (UNL)

Cell signaling (UNMC)

Neurosensory systems (UNMC)

Nanomedicine (UNMC)
Fit of Proposed Center with Other Research
at UNL & UNMC

Proposed Center would be complementary to
current research in the areas of pharmaceutical
science, combinatorial chemistry, chemical
engineering, biochemistry, molecular biology,
and environmental toxicology

A similar fit can be made with efforts in
biotechnology, food science, bioinformatics, &
general medical research or cancer research

Program would also have a good fit with several
local industries (LICOR, MDS Pharma, etc.)
History of Current COBRE Proposal from UNL

Up to three COBRE Awards allowed per institution (e.g.,
UNL has two – Virology & Redox Biology)

Only one full proposal can be submitted per institution

Current proposal was selected by UNL for development in
2007 and was submitted Oct. 24, 2007

Reviews of current proposal were received in June 2008,
with an Overall rating of “Excellent” . Final announcement
of funding will be made in Spring 2009.

If not funded this round, a revision of this proposal is
planned for the next call for COBRE proposals, which is
expected to be made in Jan/Feb 2009
Specific Proposal Submitted by UNL:
Nebraska Center for Rapid Bioanalysis (NCRB)
Overall Objectives

Creation of a Center at UNL and in cooperation with UNMC
focusing on the development of methods for the rapid analysis
and high-throughput screening of biological agents

Support and mentoring of junior faculty in the field of rapid
bioanalysis and related areas

Development and expansion of the infrastructure at UNL, UNMC
and in the state of Nebraska to support research in the field of
rapid bioanalysis

Center would be housed in Dept. Chemistry at UNL but directly
involve faculty from the Depts. of Chemical & Biomolecular
Engineering and Biological Systems Engineering at UNL, as well
as faculty in Depts. of Pharmaceutical Science and Biochemistry
& Molecular Biology at UNMC (among many others)
Specific Aims of the NCRB

Specific Aim 1: Mobilize and expand the collective
expertise at UNL and UNMC in the areas of chemistry,
biochemistry, engineering, pharmaceutical science and
basic medical research to develop, optimize, validate
and apply new technologies for rapid bioanalysis

Specific Aim 2: Establish a critical mass of
experienced researchers in the area of rapid bioanalysis
through the mentoring and training of junior
investigators, and through the targeted recruitment of
additional faculty members in this area
Specific Aims of the NCRB
(Cont’d)

Specific Aim 3: Develop/maintain an infrastructure of
support and facilities in areas such as bioinformatics and
computational chemistry, instrument development and
microfabrication, structural and functional analysis,
protein and cell production, and nanoimaging to enhance
the research capability for new and existing investigators
in the area of rapid bioanalysis
Primary Elements for Meeting the
Specific Aims of the NCRB
Administrative Core of the NCRB

PI/Program Director (D.S. Hage, UNL)

Assistant Director (Y. Lyubchenko, UNMC)

Junior Project Leaders

Mentors & Mentoring Council

External Advisory Board (EAB)

Industrial & Clinical Advisory Board (ICAB)

Core Facilities
Overall Structure of the Nebraska Center for Rapid
Bioanalysis (NCRB)
Initial Research Focus of NCRB:
Bioanalytical Tools for Drug Discovery & Biomarker Detection

Drug Discovery




Biomarker Detection




Use of proteomics, glycomics or metabolomics for drug discovery
Development of bioanalytical methods for rapidly identifying and
characterizing new drugs to target a given protein or biological pathway
Creation of high-throughput screening (HTS) methods for examining
potential drugs and for characterizing their properties
Creation of improved methods for biomarker detection/identification
Improved analysis of biomarkers for disease treatment and detection
Creation of improved methods for the study of biological pathways for
biomarker identification
Related Topics

Development of miniaturized or nanofabricated analytical systems for
drug discovery & biomarker detection
Projects by Junior Faculty

Project 1: High-Throughput Screening of Drug Candidates by NMR
(Dr. Robert Powers – Dept. Chemistry, UNL)

Project 2: Single Molecule Tracking & Imaging for High-Throughput
Screening (Dr. Greg Bashford – Dept. Biological Systems Engineering,
UNL)

Project 3: Cell Array Chips Based on Patterned Nanostructures (Dr.
Barry Cheung – Dept. Chemistry, UNL)

Project 4: Folding-Based Electrochemical Biosensors (Dr. Rebecca
Lai – Dept. Chemistry, UNL)

Project 5: Proteomic & Metabolomic Studies of a Microbial
Community (Dr. Laurey Steinke – Dept. Biochem. & Mol. Biology,
UNMC)
General relationship between Junior Projects & Theme
of High-Throughput Screening of Drugs and Biomarker
Detection
Mentoring of Junior Faculty:
The Mentoring Council

Mentoring of junior project leaders is an important part of
the COBRE program

Each Junior Project Leader is assigned three mentors




A lead mentor in an area closely related to the project
A second mentor in an area complementary to the project
Center Director or Assistant Director
Rationale behind mentor selection



One mentor for the method used in the project + one mentor for the
area of biomedical applications
At least one mentor from UNL and at least one from UNMC
Center Director or Assistant Director will be assigned based on the
location of the project and/or the area of research
Mentoring Council: Initial Members from UNL
• Dr. Ronald Cerny - mass spectrometry and applications in proteomics and the
study of small molecules (L. Steinke)
• Dr. Liangcheng Du - use of mol. biology and mass spectrometry to investigate
pathways in microorganisms and create new products (L. Steinke)
• Dr. Gerard Harbison - NMR spectroscopy (R. Powers)
• Dr. Natale (Ned) J. Ianno
- Materials research & thin film deposition; pulsed
laser deposition and sputter deposition of various materials (B. Cheung)
• Dr. Larry Parkhurst - Application of fluorescence spectroscopy in the study of
biomolecular structure and function (G. Bashford)
• Dr. Jody Redepenning - Electrochemistry and in the microfabrication of novel
devices such as chemical-modified nanoelectrodes (R. Lai)
• Dr. David S. Hage – Bioanalytical separations, affinity-based methods,
miniaturized analytical systems (R. Lai, R. Powers, L. Steinke)
Mentoring Council: Initial UNMC Members
• Dr. Kenneth W. Bayles – Microbiologist; cellular biology of S. aureus and
Bacillus anthracis as related to biofilm formation & the development of
antibiotics. (R. Powers)
• Dr. Steven H. Hinrichs – Microbiologist; interests in new antibiotics,
molecular microbiology, and use of methods such as mass spectrometry (L.
Steinke)
• Dr. Michael Hollingsworth - Microbiologist and immunologist; pancreatic
cancer and biomarkers for its detection (R. Lai)
• Dr. Ming-Fong Lin - Biochemist and pathologist; interests in prostate cancer,
cell growth regulation by tyrosine phosphorylation signal transduction and
androgen regulation of cell proliferation (B. Cheung)
• Dr. Yuri Lybuchenko – Pharmaceutical science, single molecule imaging,
fluorescence spectroscopy (G. Bashford, B. Cheung)
Evaluation & Advising of the NCRB:
The External Advisory Committee (EAC)

The EAC will consist of outstanding scientists
representing the NCRB’s key research areas will provide
an independent mechanism for evaluation of the
research projects, core facilities and activities

The EAC will also give advice on strategic planning,
including allocation of resources and the targeting of
emerging funding opportunities

The EAC meet annually on site with the Director and
Mentoring Council and provide an annual written critique
of the Center as part of the formative evaluation process
External Advisory Council (EAC)
• Dr. Susan Lunte (Univ. Kansas) – Creation of new tools for bioanalysis
based on electrochemistry, chemical separations, electrochemical sensors, and
microfabricated devices
• Dr. Fred W. McLafferty (Cornell Univ.) – Mass spectrometry & its
applications in various systems
• Dr. John L. Markley (Univ. Wisconsin) - Use of NMR spectroscopy in the
study of structural genomics, metabolomics and structure-function relationships
in proteins; multi-dimensional NMR
• Dr. Irving Wainer (NIH) - Bioanalytical chemistry, use of mass spectrometry
and chromatography in the study of biological samples
• Dr. Edward Yeung (Iowa State Univ.) - Nonlinear spectroscopy, laserbased detectors for liquid chromatography, capillary electrophoresis, single-cell
and single-molecule analysis, DNA sequencing
A Clinical & Industrial Perspective:
The Industrial & Clinical Advisory Board (ICAB)

ICAB will provide feedback regarding the NCRB’s research
portfolio, programmatic activities and center direction from
the perspective of clinical laboratories and the
pharmaceutical/biotechnology industries

This feedback will be used by the NCRB to develop contacts
for the transition of methods to the biomedical community
and provide an industrial/clinical perspective on critical
needs for drug discovery & biomarker detection

The ICAB will meet with the Center Director and Mentoring
Council annually in the spring, or six months prior
to/following the meeting of the EAC
Industrial & Clinical Advisory Board (ICAB)
• Dr. Michael Grace (Director of Bioanalytical Sciences, Bristol-Myers
Squibb) - Protein characterization, process analytical technology, biological
interaction studies and the characterization of glycoconjugates.
• Dr. James E. McClurg (Senior Vice President and Chief Scientific
Officer, MDS Pharma Services) – Pharmaceutical analysis & related
instrumentation
• Dr. John Masters (Head of Discovery Chemistry in Research &
Technology, Eli Lilly and Company) - Medicinal chemistry, development
of new analytical methods for screening of drugs and their metabolites
• Mr. Larry Middendorf (Senior Vice President of Marketing/Sales, LICOR Biosciences).- Development and marketing of new tools and
instruments for bioanalysis
• Dr. Thomas Moyer (Mayo Clinic;) - Clinical chemist ry, toxicology and
drug analysis
Facilities at UNL/UNMC in Area of Rapid
Bioanalysis

Bioinformatics & Computational Facilities.



Instrument Development/Microfabrication



Methods and tools for traditional are available through existing
facilities at UNL and UNMC (in collaboration with UNO)
More advanced computations and a cyberinfrastructure will be
available through a new Computational Core
Machine shop, and electronics shop are available at UNL
Microfabrication can be conducted in the Nanofabrication
Facility that is part of UNL’s Center for Materials Research and
Analysis
Nanoimaging

Facility available now at UNMC
Facilities at UNL/UNMC in Area of Rapid
Bioanalysis (Cont’d)

Structural & Functional Analysis





Mass spectrometry - Nebraska Center for Mass Spectrometry
(UNL) & proteomics facility at UNMC
NMR spectroscopy – UNL (Dept. Chemistry) & UNMC
Functional analysis – Biacore & DNA arrays at both UNL &
UNMC
Rapid structural analysis will be enhanced through the creation
of a new Robotics & Automated Sample Preparatio nCore
Protein & Cell Production


Facilties for protein expression, cell culturing & protein
purification in UNL, Dept. Chemical & Biomolecular Engineering
Monoconal antibody production facility at UNMC
New Core Facilities Created by NCRB

Computational Core (Hui Li - Director, UNL)
• Core will provide advanced computations and training
involving simulations and quantum chemical calculations
will be needed by some Center members (e.g., electronic
structure calculations of protein active sites, estimation of
pKa values, redox potentials, binding energies, solvation
energies, NMR chemical shifts)
• Core also will provide a cyberinfrastructure for the NCRB,
where researchers can readily exchange their data and
link into programs and data generated by other Center
facilities
New Core Facilities Created by NCRB (Cont’d)

Robotics & Automated Sample Preparation Core
(Joseph Dumais & Kurt Wulser - Directors, UNL)
• Core will provide stations that will allow the automated
preparation of samples for analysis by mass spectrometry
and/or NMR spectroscopy
• Core will be housed near the MS and NMR facilities at
UNL
• Automated sample injection systems for the highthroughput analysis of samples by NMR and mass
spectrometry will also be available through this Core
Other Components of Infrastructure
for the NCRB
• Small grants program
• Annual conference
• Monthly seminar program
• Center memberships
• Website
Proposed Future Hires under NCRB
• Junior level mass spectrometrist (proteomics, metabolomics or
associated areas) - Currently planned in Dept. Chemistry, UNL, under
PoE in Functional Genomics
• Junior level chemical engineer (biomolecular materials) Planned by UNL Dept. Chemical & Biomolecular Engineering, UNL
• Junior level analytical chemist (single molecule spectroscopy/
bioanalytical spectroscopy) - Planned by Dept. Chemistry, UNL
• Junior level pharmaceutical chemist (drug analysis/proteomics)
- Planned by Dept. Pharmaceutical Science, UNMC
• Junior level chemist/biochemist (glycomics, protein-protein
interactions or DNA-protein interactions) - Planned by Dept.
Chemistry, UNL
What will Occur During the Early Formation of
NCRB? (Year 1 - Quarter 1/Year 2)
Task
Quarter 1
Administrator
X
Mentoring Council Meetings
Internal Coordinating Committee Meetings
X
(X)
Internal Coordinating Committee Meetings
External Advisory Committee Meetingc
Quarter 3
Quarter 4
X
X
X
X
Website Development
Monthly Seminar Series
Quarter 2
X
X
X
X
X
X
X
X
X (Year 2)
Center Reviews
Formative Evaluation
X
X (Year 2)
Industrial & Clinical Advisory Board Meeting
Symposium
X
X
X (Year 2)
X
What will Occur after the Foundation of
the NCRB? (Years 1 – 5)
Benchmark
Year 1
Year 2
Hire #1 (Mass Spectrometrist)
X
X
Hire #2 (Chemical Engineer)
X
X
Year 3
Hire #3 (Analytical Chemist)
X
X
Hire #4 (Pharmaceutical Chemist)
X
X
Hire # 5 (Chemist/Biochemist)
Seed Grants
R01 Submission (Projects 1-5)
Project Turnover (Projects 1-5)
First P01 Submission (resubmission in Year
2, if needed)
Summative Evaluation (4th Quarter, Year 5)
(X)b
Year 4
Year 5
X
X
X
X
X
X
X
X
X
X
(X)c
X
X
What is Next for the NCRB COBRE Proposal?

A final decision on funding of the current proposal is
pending and expected in Spring 2009.

Preparations are underway to help address comments in
review of previous proposal in preparation for
resubmission later in 2009, if needed

Seed funds have been obtained from UNL & UNMC for
Junior Project Leader to conduct preliminary studies to
address comments of their individual proposals

Efforts to promote work and collaborations between UNL
and UNMC in the area of rapid bioanalysis, as evidenced
by this retreat