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Research Training Director’s MeetingNovember 3, 2006

Division of Basic Neuroscience and Behavioral

Research (DBNBR)

David Shurtleff, Ph.D. Director

DBNBR Goals

Identify antecedents and consequences of drug abuse and addiction

Develop and exploit new technologies, models, paradigms

Identify genetic & developmental vulnerabilities for drug abuse

Foster transdisciplinary/integrative research and training

Office of the Director David Shurtleff, PhD - Director Paul Schnur, PhD - Deputy Director Joni Rutter, PhD- Assoc Director Population & Applied Genetics Christie Baxter, BA – Program Analyst Amira Debbas, BA – Program Analyst Joyce Williams – Program Analyst

Office of the Director David Shurtleff, PhD - Director Paul Schnur, PhD - Deputy Director Joni Rutter, PhD- Assoc Director Population & Applied Genetics Christie Baxter, BA – Program Analyst Amira Debbas, BA – Program Analyst Joyce Williams – Program Analyst

TechnologyDevelopmentKaren Skinner, PhD

Deputy Director for Science and

Technology Development

TechnologyDevelopmentKaren Skinner, PhD

Deputy Director for Science and

Technology Development

TrainingCharles Sharp, PhD

Special Assistant & Training Coordinator

Beth Babecki, MA Deputy Training Coordinator

Diane Lawrence, PhD

TrainingCharles Sharp, PhD

Special Assistant & Training Coordinator

Beth Babecki, MA Deputy Training Coordinator

Diane Lawrence, PhD

Functional Neuroscience Research BranchNancy Pilotte, PhD, ChiefJerry Frankenheim, PhD

Diane Lawrence, PhDGeraline Lin, PhD

Yu (Woody) Lin, PhD

Functional Neuroscience Research BranchNancy Pilotte, PhD, ChiefJerry Frankenheim, PhD

Diane Lawrence, PhDGeraline Lin, PhD

Yu (Woody) Lin, PhD

Genetics and Molecular Neurobiology Research Branch

Jonathan Pollock, PhD, ChiefChristine Colvis, PhDJohn Satterlee, PhD

Da Yu Wu, PhD

Genetics and Molecular Neurobiology Research Branch

Jonathan Pollock, PhD, ChiefChristine Colvis, PhDJohn Satterlee, PhD

Da Yu Wu, PhD

Behavioral and CognitiveScience Research Branch

Minda Lynch, PhD, ChiefTom Aigner, PhD

Allison Chausmer, PhDSusan Volman, PhD

Cora Lee Wetherington, PhD (Women’s Health Coordinator)

Behavioral and CognitiveScience Research Branch

Minda Lynch, PhD, ChiefTom Aigner, PhD

Allison Chausmer, PhDSusan Volman, PhD

Cora Lee Wetherington, PhD (Women’s Health Coordinator)

Chemistry and Physiological Systems Research Branch

Rao Rapaka ,PhD, ChiefPaul Hillery, PhDKevin GormleyHari Singh, PhD

Pushpa Thadani, PhDDave Thomas, PhD

Chemistry and Physiological Systems Research Branch

Rao Rapaka ,PhD, ChiefPaul Hillery, PhDKevin GormleyHari Singh, PhD

Pushpa Thadani, PhDDave Thomas, PhD

Division of Basic Neuroscience and Behavioral Research

DRUGSDRUGS

BRAIN MECHANISMS

BRAIN MECHANISMS

ADDICTIONADDICTION

ENVIRONMENTENVIRONMENT

HISTORYHISTORY- previous history- expectation- learning

- previous history- expectation- learning

- social interactions- stress- conditioned stimuli

- social interactions- stress- conditioned stimuli

- genetics- circadian rhythms- disease states- gender

- genetics- circadian rhythms- disease states- gender

BIOLOGYBIOLOGY

Drug Addiction: A Complex Behavioral and Neurobiological Disorder

Dopamine

Dendritic Spines

Repeated Drug Abuse Increases Genetic Transcription Resulting in Long-term Structural

Changes

Adapted from Nestler E.J. Science & Practice Perspectives, 5(1) 2005.

Bra

nch

es

60

55

50

45

11

10

9

8CTLCTL

COC

CTL COCCTL COC

Chronic cocaine increases density of dendritic spines and neuronal branching in the nucleus

accumbens

CTL COCCTL COC CTL CTL COCCOC

Robinson, T.E. & Kolb, B. Eur. J. of Neuro. 1999. Ferrario, C.R. et al. Biol. Psychiatry, 2005.

Drug Addiction is a Developmental Disease with High Prevalence in Adolescence

NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003

Age

0.0%

0.2%

0.4%

0.6%

0.8%

1.0%

1.2%

1.4%

1.6%

1.8%

5 10 15 21 25 30 35 40 45 50 55 60 65

Perc

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each

ag

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ho d

evelo

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ep

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THCALCOHOL

TOBACCO

Highly Rewarding Effect of Nicotine/AcetaldehydeDuring Adolescence

0 1 2 3 4 5

Test Day

Nic/Acet 30/16 µg (N = 6)Acet 16 µg (N = 6)Nic 30 µg (N = 10)Saline µg (N = 8)

P90 Males

Belluzzi, et al., Neuropsychopharmacology, 2005 Apr;30(4):705-12.

*

****

****

0

10

20

30

40

0 1 2 3 4 5

Test Day

Mean

Self

-In

jecti

on

s (

Nose-p

okes in

3 h

r)

Nic/Acet 30/16 µg (N=11)Acet 16 µg (N = 8)Nic 30 µg (N=9)Saline 100 µl (N=7)

P27 Males

Drug Addiction Is Influenced by Interactions of Genes and Environment

Twin studies consistently show

that there is a heritable component

to drug abuse and addiction.

What are the gene variants?

Extramural StudyNIDA/Perlegen/WashUWhole Genome Scan for Nicotine Addiction

Intramural StudyNIDA

Affymetrix 500K screen for Drug Addiction

Many of These Genes Have Synaptic Functions

Dean and Dresbach, TINS, 2006

{

presynaptic

postsynaptic

{

De Camilli et al, 2001

Dendritic Spines

CELL ADHESION

NEURO-TRANSMISSION

SIGNAL TRANSDUCTION

TRANSCRIPTION FACTORS

Genome-wide association scans

Gene variants

What is the functionalsignificance?

Need: Functional validation of gene variant

Capitalize on:NIH Knockout Mouse Project

High-throughput genetic and RNAi methods

Research in GEI (FY11&12)

Use genetic models to:

Investigate mechanisms of drug dependence

Test potential therapeutics

Functional Genomics

Addiction is a Complex Behavioral, Neurobiological, and Genetic Disorder

Addiction is a Complex Behavioral, Neurobiological, and Genetic Disorder

ENVIRONMENT & DRUGEXPOSURE

SYNAPTIC PLASTICITY

BRAINCHANGES

GENETIC VARIANTS

DBNBR Research Training

Framework to enhance cooperative activities among 16 NIH Institutes and Centers

Take on challenges in neuroscience that are best met collectively

Develop research tools and infrastructure that will serve the entire neuroscience community

Research Training Programs

Training in Neuroscience Imaging (Steve Grant, PO)Computational Neuroscience (Susan Volman, PO)Neurobiology of Disease (Beth Babecki, PO)Jointly Sponsored Predoctoral Program in the Neurosciences (JSPTPN)

(Beth Babecki, PO)

NIH Roadmap FOR Medical Research

TransNIH initiative for a more efficient and productive system of medical research

Identifies themes in three main areas for support:

New pathways to discoveryResearch teams of the futureRe-engineering the clinical research enterprise

• NIDA lead on Interdisciplinary Research Training initiative– Support didactic and research experiences designed to provide

students with the knowledge and research experiences necessary to develop interdisciplinary solutions

– Allison Chausmer (lead program officer)

Career Development Plan

Yes

Do I have pilot data?No

No

Apply for R03, BSTART or ISTART

Do I need more training or changing career emphasis?

Institutional Pre-Doctoral Fellowship-T32

Pre-Doctoral Fellowship-F31

Post-Doctoral Fellowship-F32

Institutional Post-Doctoral Fellowship-T32

R01

YesApply for Mentored

K

****

****

****

* Contact Program* Contact Program

Mentored Career Development Awards

Mentored Research Scientist Development Award (K01)

NIH Pathway to Independence (PI) Award (K99/R00)

Mentored Clinical Scientist Development Award (K08)

Mentored Quantitative Research Career Development Award (K25)

Mentored Patient-Oriented Research Career Development Award (K23)

Progress Review of T32s

Trainee progress (publications, placement, mentors)

Program features and changes (breadth, student diversity, scientific diversity)

Interactions

Scientific

Career development

Use of slots (level, length, throughput, transition to independence)

Contingency planning for gaps in funding (last year of T32)- Looking beyond supplements

Enhancing the Training Experience

Scientific MeetingsNIDA/SfN Mini-convention

Poster presentation

Travel awards

NetworkingCPDD/ INRC/ SNIP etc. training mixers

NIDA/SfN Mini-convention/NIDA exhibit

GrantsmanshipCPDD Grant writing workshop/tutorial

SFN NIH Professional “Survival” Skills Workshop

NIDA-supported Scientific TrainingCold Spring Harbor

Summer Institute

Woods Hole

DBNBR Training Coordinators

Charles Sharp: csharp1@nida.nih.gov

- -

301-443-1887

Beth Babecki: bbabecki@nida.nih.gov

301-443-1887

Diane Lawrence: LawrenceDi@nida.nih.gov

301-443-1887