NIGMS Training inNIGMS Training inSystems & Integrative Systems & Integrative ScienceScience

Peter C. Preusch, Ph.D.Program Director

Pharmacological Sciences Training Grant Program, NIGMS, NIH

LSRO MeetingBethesda Marriott HotelOctober 20-21, 2002

NIGMS and NIH NIGMS and NIH Predoctoral & Predoctoral & Postdoctoral Training in Postdoctoral Training in FY2001FY2001

Predoc NIGMS Other NIH NIH

Trainees 3122 4730 7852

Fellows 122 788 910

Total 3244 5518 8762

Postdoc NIGMS Other NIH NIH

Trainees 157 5254 5411

Fellows 404 1420 1824

Total 561 6674 7235

Total U.S.BiolSci 52,629Clin Med 15,846

Total U.S.BiolSci 16,093Clin Med 11,280

OD/NIGMS 11/13/01 http://grants1.nih.gov/training/data/tf_trends/sld009.htmNSF-NIH Survey of Graduate Students and Postdocs in Science and Engineering in 2000

http://grants1.nih.gov/training/data/tf_trends/sld006.htm

Postdoc TraineesPredoc Trainees

GM GM

Other NIH Other NIH

NIGMS Mechanisms of NIGMS Mechanisms of Training and Research Training and Research SupportSupport

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

NIGMS Training ProgramsNIGMS Training ProgramsPredoctoral Trainees (Awards) Predoctoral Trainees (Awards) FY2001FY2001

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 10/30/2001excludes short-term training awards

NIGMS Training NIGMS Training ProgramsProgramsPostdoctoral Trainees Postdoctoral Trainees FY2001FY2001Anesthesiology 21

Clinical Pharmacology 31

Medical Genetics 39

Trauma and Burn 66

157

OD/NIGMS 11/13/01

NRSA Postdoctoral NRSA Postdoctoral Fellowships (F32, F33)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

NIH PRAT and CLINPRAT NIH PRAT and CLINPRAT FellowshipsFellowships

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

NIGMS Career NIGMS Career Development Awards Development Awards (FY2001)(FY2001)

Applications 29New Awards 7Active 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

What is training in What is training in the the Pharmacological Pharmacological Sciences ?Sciences ?

Pharmacology Physiology Toxicology Pharmaceutical Chemistry Pharmaceutics Medicinal Chemistry Chemistry Biochemistry, Molecular, and

Cell Biology Structural Biology/Biophysics

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

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.

What is training in What is training in Systems and Systems and Integrative Biology?Integrative Biology?

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

Biology

Organ/Systems Physiology Complex Biological Problems Quantitative Approaches Computational Simulations

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.

What are we training What are we training Medical Scientists to Medical Scientists to do?do?

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

Bioethics Biostatistics Bioengineering Economics Epidemiology Public Health

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.

NIGMS Predoc Trainees

0

200

400

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1000F

Y1986

1987

1988

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1990

1991

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1993

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1997

1998

1999

2000

2001

MS

CM

GN

SI

MB

PS

BT

CB

JT

Distribution of Slots by ProgramDistribution of Slots by Program

Distribution of Distribution of Training Grants by Training Grants by ProgramProgramFY1996 1997 1998 1999 2000 2001

PS 31 30 32 31 26 25SIB 31 31 31 30 30 30MSTP 31 32 33 35 37 39CBI 13 13 13 15 16 15CM 47 45 47 47 48 46MB 30 31 31 30 26 27GN 33 32 33 33 33 34BT 20 21 18 17 16 17BI 0 0 0 0 0 3Total 236 235 238 238 232 236

19

75

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75

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19

75

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75

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77

19

77

19

78

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78

19

78

19

78

19

79

19

79

19

78

19

79

19

79

19

82

19

84

19

88

19

90

19

90

19

92

19

94

19

92

19

97

19

96

19

98

19

98

20

01

20

01

20

01

1975

1980

1985

1990

1995

2000

2005

2010

Ca

lend

ar Y

ear

Year of Grant Start

History of Pharmacological Sciences Training Grants

What is meant by What is meant by Systems &Integrative Systems &Integrative Pharmacology?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?

Fraction of Trainees using Fraction of Trainees using Animal Models or Human Animal Models or Human SubjectsSubjects

Continuing Grants FY2001

Ended2000-01

New2001

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41

What counts as What counts as research training in research training in drug metabolism?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

00.10.20.30.40.50.60.7

1 3 5 7 9 11 13 15 17 19 21 23 25

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

Predoctoral PharmSciPredoctoral PharmSci Trainees in Drug Trainees in Drug MetabolismMetabolism% of trainees reported

Why we held the Why we held the meeting?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

Goals of the Goals of the Meeting Meeting

NIGMS Pharmacological Sciences Training Grant Meeting:

What is Training in the Pharmacological Sciences?

Goals:

1. Increase scientific diversity of PS program portfolio.a) Balance between molecular/cellular and systems/integrative trainingb) Inclusion of traditionally allied disciplinesc) Inclusion of newly emerging disciplinesd) Inclusion of industrial and clinical experiencese) Inclusion of new student pools, e.g., MD, PharmD, DVM

2. Define core knowledge that makes the PS program distinct.

3. Improve communication between potential applicants, reviewers, current

trainers, and NIH staff.

Addressing the Issues:Addressing the Issues:Old Schools, New Schools, Old Schools, New Schools, New PoolsNew 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

Distribution of Schools by Types of Training Grant Awarded (FY2001)

PS & SIB & MSTP

PS & SIB

PS & MSTP

PS

SIB & MSTP

MSTP

SIB

Other NIGMS

NIGMS funded Schools by PS Support and Colleges Located on Campus (FY2001)

PS & Med

PS & Med & Pharm

PS & Med & Pharm & Vet

PS & Med & Vet

PS & VetMedMed & Pharm

Med & Pharm & Vet

Med & Vet

Pharm & Vet

Vet

Pharm

A&S

96 Non-NIGMS Schools of Medicine, Pharmacy, and/or Vet Medicine

Med & Pharm & Vet, 1

Med & Pharm, 25

Med & Vet, 1

Pharm & Vet, 3

Vet, 9

Pharm, 20

Med, 29

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

Hypothesis: MD Hypothesis: MD training and PhD training and PhD training are linked.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?

Hypothesis: Hypothesis: Pharmacy contributes Pharmacy contributes much to the diversity much to the diversity of PS trainingof 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

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

Major Points of Major Points of DiscussionDiscussion

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.

Major Points Major Points (Continued)(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.

PS Training PS Training OutcomesOutcomesWhat do academia, industry, What do academia, industry, and trainees value most?and trainees value most?

Problem solving, self-learning, communication, collaboration.

What factors What factors determine trends in determine trends in Graduate Training?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?

What is NIGMS Looking What is NIGMS Looking For?For?Review Criteria: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

What is NIGMS Looking What is NIGMS Looking For?For?Room for All under the Room for All under the UmbrellaUmbrella 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.

Will the pendulum Will the pendulum return of its own return of its own accord?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?

NIGMS Training Grant NIGMS Training Grant InformationInformation

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