NIGMS Training in Systems & Integrative Science

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NIGMS Training inSystems Integrative Science

• Peter C. Preusch, Ph.D.
• Program Director
• Pharmacological Sciences Training Grant Program,
  NIGMS, NIH

LSRO Meeting Bethesda Marriott Hotel October
20-21, 2002
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NIGMS and NIH Predoctoral Postdoctoral Training
in FY2001
Total U.S. BiolSci 52,629 Clin Med 15,846
Total U.S. BiolSci 16,093 Clin Med 11,280
OD/NIGMS 11/13/01 http//grants1.nih.gov/training
/data/tf_trends/sld009.htm NSF-NIH Survey of
Graduate Students and Postdocs in Science and
Engineering in 2000
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GM
GM
Other NIH
Other NIH
http//grants1.nih.gov/training/data/tf_trends/sld
006.htm
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NIGMS Mechanisms of Training and Research Support

• Training Grants
• Predoctoral (T32) Institutional NRSA
• Postdoctoral (T32) Institutional NRSA
• NRSA Fellowships (F32) Postdoctoral
• NIH PRAT ClinPRAT Postdoctoral
• Career Development Awards (K08, K23, K25)
• Research and Research Supplements
• R01, P01, P50, R15, R21, R24, R41-R43, U54
• Minority Opportunities in Research

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NIGMS Training ProgramsPredoctoral Trainees
(Awards) FY2001

• Cellular and Molecular Biology 789 (46)
• Genetics 398 (34)
• Systems and Integrative Biology 247 (30)
• Pharmacological Sciences 202 (25)
• Molecular Biophysics 221 (27)
• Biotechnology 178 (17)
• Chemistry/Biology Interface 113 (15)
• Joint Training in Neuroscience 17 (1)
• Bioinformatics and Computational Biol 10 (3)
• Medical Scientist 927 (39)
• 3102 (237)

NIGMS Active Predoctoral NRSA Trainees
10/30/2001 excludes short-term training awards
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NIGMS Training ProgramsPostdoctoral Trainees
FY2001

• Anesthesiology 21
• Clinical Pharmacology 31
• Medical Genetics 39
• Trauma and Burn 66
• 157

OD/NIGMS 11/13/01
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NRSA Postdoctoral Fellowships (F32, F33)

• Where are the Systems Biologists?
• FY2001 NIGMS Pharm(P640)
  Physiol(644)
  
• Apps 429 4 (0.9)
  2 (1.2)
• New Awards 165 2 (1.2) 1
  (0.6)
• Active 424 13 (3.0)
  3 (0.7)
• Active RPGs 4185 241 (5.8) 266
  (6.4)
• R01,R37,R21,R55,R29,PO1,P50
  P140, P141, P142, P143 P144, P145, P146

Source IMPACII QVR search by mechanism and PAC -
PCP Fall, 2002
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NIH PRAT and CLINPRAT Fellowships

• Pharmacology Research Associate Training
• Supports Postdoctoral Fellows in NIH Intramural
  Labs
• 18 Applications
• 8 New Awards
• 15 Active Fellowships
• Clinical Pharmacology Res Assoc Training
• Supports MD Fellows at NIH Clinical Center
• 5-6 Applications
• 1-2 New Awards
• 4 Active Fellowships

Source Program Directors
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NIGMS Career Development Awards (FY2001)

• Applications 29
• New Awards 7
• Active Grants 21
• K08 Mentored Clinical Scientist Award in
  Anesthesiology, Clinical Pharmacology, and Trauma
  and Burn Injury
• K23 Mentored Patient Oriented RCDA
• K25 Mentored Quantitative RCDA

Source IMPACII QVR Search by mechanism - PCP
Fall, 2002
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What is training in the Pharmacological Sciences
?
Interdisciplinary training in pharmacology and
related disciplines relevant to the discovery and
development of therapeutic agents and to the
basic understanding of drug targets and
mechanisms of action.

• Neurobiology
• Psychiatry
• Immunology
• Microbiology
• Virology
• Pathology
• Cancer Biology
• Experimental Therapeutics
• Medicine
• Veterinary Medicine

• Pharmacology
• Physiology
• Toxicology
• Pharmaceutical Chemistry
• Pharmaceutics
• Medicinal Chemistry
• Chemistry
• Biochemistry, Molecular, and Cell Biology
• Structural Biology/Biophysics

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What is training in Systems and Integrative
Biology?
Interdisciplinary training in the integrative,
regulatory, and developmental processes of higher
organisms and the functional components of these
processes. Integration of approaches from the
molecular and cellular to the whole organism and
its behaviors.

• Organ/Systems Physiology
• Complex Biological Problems
• Quantitative Approaches
• Computational Simulations

• Physiology
• Biomedical Engineering
• Neurosciences
• Behavioral Sciences
• Clinical Sciences
• Biochemistry
• Cell and Developmental Biology

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What are we training Medical Scientists to do?
The Medical Scientist Training Program (MSTP)
supports combined MD/PhD degree training in any
area scientific area with the objective of
creating scientists who can bridge basic and
clinical research.

• Biological Sciences
• Chemical Sciences
• Physical Sciences
• Social Sciences
• Behavioral Sciences
• Computer Sciences

• Bioethics
• Biostatistics
• Bioengineering
• Economics
• Epidemiology
• Public Health

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Distribution of Slots by Program
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Distribution of Training Grants by Program
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What is meant by Systems Integrative
Pharmacology?

• Where is the line?
• Human in vivo study?
• Animal in vivo study?
• Animal in situ preps?
• Human subject sample?
• Animal tissue samples?
• Primary cell cultures?
• Cells, genes, proteins?
• In silico research?
• Do we have a problem?

• Which models count?
• Primate, rodent, frog, fish, fly, worm, yeast?
• What constitutes an integrative response?
• Integrated by system or by disease?
• Who does the integrating - the system or the
  pharmacologist?

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Fraction of Trainees using Animal Models or Human
Subjects
Ended 2000-01
New 2001
Continuing Grants FY2001
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What counts as research training in drug
metabolism?

• ADME
• Pharmacokinetics
• Metabolite Identification
• Prodrug Activations
• Phase I II Enzymes
• Drug Transporters
• Structure/Function
• SAR
• Expression Levels
• Regulation

• synthesis and reactivity
• chemical models
• homogenates, fractions, purified proteins
• cell cultures
• perfused tissues and intact animal human
• activity antibody assays
• matrix arrays
• in silico simulations

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Predoctoral PharmSci Trainees in Drug Metabolism
NIGMS Predoctoral Training in Pharmacological
Sciences N 26 in FY2002 Slots 203 Reported
students 358 Drug Metabolism 41 Drug
Metabolism Ave 11.5 of trainees Est slots
1/3 - 1/5 total pool Est total Drug
Metabolism predoctoral students 70 - 117
of trainees reported
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Why we held the meeting?

• Decline in number of funded PS programs
• Loss of program strength in in vivo methods
• Loss of program strength in toxicology
• Loss of programs in schools of pharmacy
• Narrowing scope of research training offered
• Changes in medical education landscape
• Changes in graduate school admissions
• Concerns about balance between old and new
• Concerns about overlap with other programs

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Goals of the Meeting

• NIGMS Pharmacological Sciences Training Grant
  Meeting
• What is Training in the Pharmacological Sciences?
• Goals
• Increase scientific diversity of PS program
  portfolio.
• Balance between molecular/cellular and
  systems/integrative training
• Inclusion of traditionally allied disciplines
• Inclusion of newly emerging disciplines
• Inclusion of industrial and clinical experiences
• Inclusion of new student pools, e.g., MD,
  PharmD, DVM
• Define core knowledge that makes the PS program
  distinct.
• Improve communication between potential
  applicants, reviewers, current trainers, and NIH
  staff.

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Addressing the IssuesOld Schools, New Schools,
New Pools

• Solution 1 Utilize the existing programs
• currently funded PS, SIB, and MSTP grants
• Solution 2 Attract new PS programs from
  existing NIGMS funded schools
• 33 have PS grants
• 82 have schools of med, pharm, or vet
• Solution 3 Attract new PS programs from
  currently non-NIGMS funded schools
• Wide open field - all your best can be PS
• 96 Schools of Med, Pharm, or Vet Med
• Solution 4 Undergraduate Pharmacology

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Hypothesis The PhD degree experience in a
medical school should be different from a
non-medical school PhD.

• What does your program do to take unique
  advantage of its affiliation with a medical
  school?
• What are your students doing that they could not
  be doing in a College of Agriculture or Science?
• What are they learning about the interface
  between basic research and clinical practice?
• What opportunities exist for your students to
  participate in clinical research?

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Hypothesis MD training and PhD training are
linked.

• How have changes in MD training changed
  instruction in pharmacology for your MDs and for
  your PhD students?
• What role do MDs play in training your PhD
  students?
• What are you doing to prepare your students for
  their role in training MDs?

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Hypothesis Pharmacy contributes much to the
diversity of PS training

• Medicinal Chemistry, Pharmaceutics, and
  Pharmaceutical Chemistry extend the breadth of PS
  programs in biophysical, chemical, and physical
  sciences.
• Pharmaceutics and Clinical Pharmacy extend PS
  programs in the area of drug discovery and drug
  development.
• Pharmacokinetics, pharmacodynamics, drug
  delivery, drug-drug interactions are of major
  interest in pharmacy schools.
• PharmD students and PharmD/PhD students bring a
  different set of skills to bear and are more
  likely to work with human subjects - the ultimate
  experimental systems and integrative model

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Hypothesis PhD students in a Vet School are
more likely to work with animals.

• Involving Vet Schools may improve training in
  Systems Integrative Pharmacology
• What work are your students doing that they would
  not do, if they were not associated with a Vet
  School?
• What unique contributions can DVMs, PhDs, and
  DVM/PhDs make to science?

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Major Points of Discussion

• Pharmacology is the core discipline in which all
  PS students should receive training.
• Pharmacokinetics and Pharmacodynamics remain the
  core subjects of pharmacology.
• Systems and Integrative Pharmacology (in vivo
  whole animal) is in demand, but in trouble.
• State-of-the-art training follows from the
  research interests of a research active faculty.
• New science (e.g., genomics, proteomics, and
  bioinformatics) needs to be included, but must be
  connected to old roots.

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Major Points (Continued)

• Scientific Diversity in research should be a
  natural outcome of the varied strengths of U.S.
  institutions.
• Scientific Diversity in student pools is
  desirable and may achieved by reaching out across
  campus.
• Inclusion of a clinical experience in some
  programs would be an innovation, but is not easy
  or sufficient.
• Inclusion of an industrial experience would be a
  useful option, but should not be mandatory.
• Changes in the medical curriculum have resulted
  in new separate graduate courses at most
  institutions.
• Changes to umbrella admissions and 1st year core
  courses have required major changes in programs.

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PS Training OutcomesWhat do academia, industry,
and trainees value most?
Problem solving, self-learning, communication,
collaboration.
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What factors determine trends in Graduate
Training?

• University administration and faculty interests
• What's hot? Who's retiring? Who are you
  hiring?
• Industrial and academic job opportunities
• What's hot? What's needed? What will be needed
  in 10 years?
• Student application numbers
• What's interesting or at least financially
  rewarding?
• Peer reviewer judgments
• What constitutes good training?
• NIGMS supports only a fraction of the total
  trainees
• NIGMS support leverages other support?
• NIGMS support affects application numbers,
  recruitment?
• NIGMS review process affects university
  decisions?

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What is NIGMS Looking For?Review Criteria

• Strong research faculty
• Cutting-edge, peer-reviewed, science
• Strong student pool
• Depth, breadth, quality, critical mass
• Current trainees and training record
• Training Program
• Courses, rotations, exams, monitoring, mentoring,
  enrichment, breadth and depth of opportunities.
• Recruitment of under-represented minorities
• Training in responsible conduct of research

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What is NIGMS Looking For?Room for All under the
Umbrella

• NIGMS supports interdisciplinary training.
• Pharmacology is central to the PS Program, but
  should not be exclusive.
• Diversity is good - programs should NOT all look
  alike!
• Potential Strengths Mol Pharm, Clin Pharm, Med
  Chem, Toxicol, Pharmacy, Therapeutics
• NIGMS would welcome new programs that embrace
  DVM, PharmD, other new pools.

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Will the pendulum return of its own accord?

• Transgenic and knock-out rodents?
• Pharmacogenetic human phenotyping?
• Bioinformatics Pharmacogenomics?
• Behavioral and neurosciences studies?
• Chemical biology drug design?
• Imaging methods in drug development?
• Human studies vs animal models?
• Emphasis on translational research?
• Law of supply and demand?

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NIGMS Training Grant Information

• http//www.nigms.nih.gov/funding/trngmech.html
• Pharmacological Sciences
• Peter C. Preusch - 301-594-5938
• Systems and Integrative Biology
• Alison E. Cole - 301-594-3349
• Medical Scientist Training Program
• Bert Shapiro - 301-594-3830
• NIGMS Assistant Director for Training
• John Norvell - 301-594-0533