Research Training Director’s Meeting November 3, 2006 Division of Basic Neuroscience and Behavioral Research (DBNBR) David Shurtleff, Ph.D. Director
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
en
tag
e in
each
ag
e g
rou
p w
ho d
evelo
p
firs
t -tim
e d
ep
en
den
ce
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.
*
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****
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: [email protected]
- -
301-443-1887
Beth Babecki: [email protected]
301-443-1887
Diane Lawrence: [email protected]
301-443-1887