NIGMS Programs for Biotechnology

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NIGMS Training in

Systems & 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

NIGMS and NIH Predoctoral &
Postdoctoral Training in FY2001

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


52,629

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

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

Postdoc Trainees
Predoc Trainees
GM

GM

Other NIH

Other NIH

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




NIGMS Training Programs

Predoctoral 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

NIGMS Training Programs

Postdoctoral Trainees FY2001

Anesthesiology





21

Clinical Pharmacology



31


Medical Genetics




39

Trauma and Burn




66









157

OD/NIGMS 11/13/01

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

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

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

What is training in the

Pharmacological 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 Systems
and 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
Medical Scientists to 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
600
800
1000
FY1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
MS
CM
GN
SI
MB
PS
BT
CB
JT
Distribution of Slots by Program

Distribution of Training
Grants by Program

FY1996
1997
1998
1999
2000
2001
PS
31
30
32
31
26
25
SIB
31
31
31
30
30
30
MSTP
31
32
33
35
37
39
CBI
13
13
13
15
16
15
CM
47
45
47
47
48
46
MB
30
31
31
30
26
27
GN
33
32
33
33
33
34
BT
20
21
18
17
16
17
BI
0
0
0
0
0
3
Total
236
235
238
238
232
236
1975
1975
1975
1975
1975
1975
1975
1975
1975
1975
1975
1975
1975
1975
1975
1977
1977
1978
1978
1978
1978
1979
1979
1978
1979
1979
1982
1984
1988
1990
1990
1992
1994
1992
1997
1996
1998
1998
2001
2001
2001
1975
1980
1985
1990
1995
2000
2005
2010
Calendar Year
Year of Grant Start
History of Pharmacological Sciences Training Grants
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?


Fraction of Trainees using Animal
Models or Human Subjects

Continuing Grants
FY2001

Ended

2000
-
01

New

2001

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 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




0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
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 PharmSci


Trainees in Drug Metabolism

% of trainees reported

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

Goals of the 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 training

b)
Inclusion of traditionally allied disciplines

c)
Inclusion of newly emerging disciplines

d)
Inclusion of industrial and clinical experiences

e)
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:

Old 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

Distribution of Schools by Types
of Training Grant Awarded (FY2001)
PS & SI B & MSTP
PS & SI B
PS & MSTP
PS
SI B & MSTP
MSTP
SI B
Ot her NI GMS
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 & Vet
Med
Med & 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:
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?

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?



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



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?


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.

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.



PS Training Outcomes

What do academia, industry, and
trainees value most?

Problem solving, self
-
learning, communication, collaboration.

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?

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


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.



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?


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