Group Meeting

1
Group Meeting

• July 21, 2005

2
Proposed Topics

• Overview of projects
• Future directions for the lab
• Strategies for success at the bench
• When to submit
• Nitty-gritty of running an academic lab

3
Proposed Topics

• Overview of projects
• Future directions for the lab
• Strategies for success at the bench
• When to submit
• Nitty-gritty of running an academic lab

4
Overview of projects

• Technology development
• Mechanisms of plasticity
• Mechanisms of HD

5
Technology development

• Motivation
• Question-driven
• Novelty
• Immediate projects
• Add capacity (2nd system)
• Add power (spectral imaging, focusing,
  optics)
• Ease of use (acquisition, analysis)
• Propagate technology

6
Mechanisms of Plasticity

• Overarching biological question
• What are the experience-dependent mechanisms by
  which the neurons achieve long-term adaptive
  responses?

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Mechanisms of Plasticity

• What are the signaling cascades that couple
  extracellular synaptic signals to intracellular
  biochemistry
• NMDAR reconstitution, AMPAR modulation, PKD, BDNF
  (Sarah, Vikram)
• How are these signals integrated within the
  nucleus or at the synapse to produce meaningful
  responses?
• HDACs, Arc transcription, Arc function (Carol,
  Renatta, Sean, Vikram)
• How is synapse-specificity preserved?
• Arc mRNA transport, Arc function (Carol, Maya,
  Renatta, Sean, Vikram)

18
Mechanisms of HD

• Overarching biological question
• What are the mechanisms by which polyglutamine
  expansion in huntingtin lead to HD?

19
Mechanisms of HD
20
Mechanisms of HD

• What are the toxic species of mutant htt?
• Epitope mapping (3B5H10), crystallography, FRET
  (Preethi, Kenny, Clare, Montse, Jason, Sid)
• What cellular changes predict htt-induced
  degeneration?
• Proteasome dysfunction, autophagy, (Sid, Jason,
  Quinzi)
• What is the basis for neuron-specific death in
  HD?
• Enkephalin ttA HD mice (Montse)
• Is HD due to death or dysfunction? What is htts
  normal function?
• Calcium signaling, synaptic vesicle turnover
  (Daniel)

21
Proposed Topics

• Overview of projects
• Future directions for the lab
• Strategies for success at the bench
• When to submit
• Nitty-gritty of running an academic lab

22
Technology development

• Really, really big picture - a tool to do
  systems cell biology
• Established the central idea
• Spectral imaging
• Fully-automated forms of analysis
• New probes
• In vivo

23
Mechanisms of Plasticity

• Lentivirus
• Low-risk approach to creating KOs, TGs
• Means to population-based biochemistry (e.g.,
  proteomics, microarrays)
• In vivo approaches
• Multiphoton imaging
• Behavior
• Build bridges to systems NS
• (manipulate selected circuits/space/time)

24
Mechanisms of HD

• Awesome power of mammalian! genetics
• Combine genome-wide siRNA (or cDNA
  overexpression) screens with
• throughput robotic microscopy
• Chemical genetics (cure HD, why not?)
• LDDN
• New fluorescent probes that report neuronal
  function

25
Proposed Topics

• Overview of projects
• Future directions for the lab
• Strategies for success at the bench
• When to submit
• Nitty-gritty of running an academic lab

26
Strategies for Success at the Bench

1. Find a question that genuinely excites you
2. Know and invest in yourself, learn how you learn
   best
3. Experimental design Simple, simple, simple, but
   not too simple
4. Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!
   !!!!!!!!!!!)
5. Design your experiment with the end in mind
6. Fail fast, so you can succeed
7. Regarding new techniques, be fearless but not
   stupid
8. A year in the lab can save a week in the library
9. Apply principles of good time-management budget
   your time, be disciplined, work hard but take
   breaks too
10. Efficient with things, effective with people
11. Interact! Discussion and collaboration can be the
    quickest way to significance and its fun

27
Strategies for Success at the Bench

1. Find a question that genuinely excites you
2. Know and invest in yourself, learn how you learn
   best
3. Experimental design Simple, simple, simple, but
   not too simple
4. Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!
   !!!!!!!!!!!)
5. Design your experiment with the end in mind
6. Fail fast, so you can succeed
7. Regarding new techniques, be fearless but not
   stupid
8. A year in the lab can save a week in the library
9. Apply principles of good time-management budget
   your time, be disciplined, work hard but take
   breaks too
10. Efficient with things, effective with people
11. Interact! Discussion and collaboration can be the
    quickest way to significance and its fun

28
Strategies for Success at the Bench

1. Find a question that genuinely excites you
2. Know and invest in yourself, learn how you learn
   best
3. Experimental design Simple, simple, simple, but
   not too simple
4. Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!
   !!!!!!!!!!!)
5. Design your experiment with the end in mind
6. Fail fast, so you can succeed
7. Regarding new techniques, be fearless but not
   stupid
8. A year in the lab can save a week in the library
9. Apply principles of good time-management budget
   your time, be disciplined, work hard but take
   breaks too
10. Efficient with things, effective with people
11. Interact! Discussion and collaboration can be the
    quickest way to significance and its fun

29
Strategies for Success at the Bench

1. Find a question that genuinely excites you
2. Know and invest in yourself, learn how you learn
   best
3. Experimental design Simple, simple, simple, but
   not too simple
4. Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!
   !!!!!!!!!!!)
5. Design your experiment with the end in mind
6. Fail fast, so you can succeed
7. Regarding new techniques, be fearless but not
   stupid
8. A year in the lab can save a week in the library
9. Apply principles of good time-management budget
   your time, be disciplined, work hard but take
   breaks too
10. Efficient with things, effective with people
11. Interact! Discussion and collaboration can be the
    quickest way to significance and its fun

30
Strategies for Success at the Bench

1. Find a question that genuinely excites you
2. Know and invest in yourself, learn how you learn
   best
3. Experimental design Simple, simple, simple, but
   not too simple
4. Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!
   !!!!!!!!!!!)
5. Design your experiment with the end in mind
6. Fail fast, so you can succeed
7. Regarding new techniques, be fearless but not
   stupid
8. A year in the lab can save a week in the library
9. Apply principles of good time-management budget
   your time, be disciplined, work hard but take
   breaks too
10. Efficient with things, effective with people
11. Interact! Discussion and collaboration can be the
    quickest way to significance and its fun

31
Strategies for Success at the Bench

1. Find a question that genuinely excites you
2. Know and invest in yourself, learn how you learn
   best
3. Experimental design Simple, simple, simple, but
   not too simple
4. Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!
   !!!!!!!!!!!)
5. Design your experiment with the end in mind
6. Fail fast, so you can succeed
7. Regarding new techniques, be fearless but not
   stupid
8. A year in the lab can save a week in the library
9. Apply principles of good time-management budget
   your time, be disciplined, work hard but take
   breaks too
10. Efficient with things, effective with people
11. Interact! Discussion and collaboration can be the
    quickest way to significance and its fun

32
Strategies for Success at the Bench

1. Find a question that genuinely excites you
2. Know and invest in yourself, learn how you learn
   best
3. Experimental design Simple, simple, simple, but
   not too simple
4. Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!
   !!!!!!!!!!!)
5. Design your experiment with the end in mind
6. Fail fast, so you can succeed
7. Regarding new techniques, be fearless but not
   stupid
8. A year in the lab can save a week in the library
9. Apply principles of good time-management budget
   your time, be disciplined, work hard but take
   breaks too
10. Efficient with things, effective with people
11. Interact! Discussion and collaboration can be the
    quickest way to significance and its fun

33
Strategies for Success at the Bench

1. Find a question that genuinely excites you
2. Know and invest in yourself, learn how you learn
   best
3. Experimental design Simple, simple, simple, but
   not too simple
4. Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!
   !!!!!!!!!!!)
5. Design your experiment with the end in mind
6. Fail fast, so you can succeed
7. Regarding new techniques, be fearless but not
   stupid
8. A year in the lab can save a week in the library
9. Apply principles of good time-management budget
   your time, be disciplined, work hard but take
   breaks too
10. Efficient with things, effective with people
11. Interact! Discussion and collaboration can be the
    quickest way to significance and its fun

34
Strategies for Success at the Bench

1. Find a question that genuinely excites you
2. Know and invest in yourself, learn how you learn
   best
3. Experimental design Simple, simple, simple, but
   not too simple
4. Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!
   !!!!!!!!!!!)
5. Design your experiment with the end in mind
6. Fail fast, so you can succeed
7. Regarding new techniques, be fearless but not
   stupid
8. A year in the lab can save a week in the library
9. Apply principles of good time-management budget
   your time, be disciplined, work hard but take
   breaks too
10. Efficient with things, effective with people
11. Interact! Discussion and collaboration can be the
    quickest way to significance and its fun

35
Strategies for Success at the Bench

1. Find a question that genuinely excites you
2. Know and invest in yourself, learn how you learn
   best
3. Experimental design Simple, simple, simple, but
   not too simple
4. Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!
   !!!!!!!!!!!)
5. Design your experiment with the end in mind
6. Fail fast, so you can succeed
7. Regarding new techniques, be fearless but not
   stupid
8. A year in the lab can save a week in the library
9. Apply principles of good time-management budget
   your time, be disciplined, work hard but take
   breaks too
10. Efficient with things, effective with people
11. Interact! Discussion and collaboration can be the
    quickest way to significance and its fun

36
Strategies for Success at the Bench

1. Find a question that genuinely excites you
2. Know and invest in yourself, learn how you learn
   best
3. Experimental design Simple, simple, simple, but
   not too simple
4. Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!
   !!!!!!!!!!!)
5. Design your experiment with the end in mind
6. Fail fast, so you can succeed
7. Regarding new techniques, be fearless but not
   stupid
8. A year in the lab can save a week in the library
9. Apply principles of good time-management budget
   your time, be disciplined, work hard but take
   breaks too
10. Efficient with things, effective with people
11. Interact! Discussion and collaboration can be the
    quickest way to significance and its fun

37
Strategies for Success at the Bench

1. Find a question that genuinely excites you
2. Know and invest in yourself, learn how you learn
   best
3. Experimental design Simple, simple, simple, but
   not too simple
4. Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!
   !!!!!!!!!!!)
5. Design your experiment with the end in mind
6. Fail fast, so you can succeed
7. Regarding new techniques, be fearless but not
   stupid
8. A year in the lab can save a week in the library
9. Apply principles of good time-management budget
   your time, be disciplined, work hard but take
   breaks too
10. Efficient with things, effective with people
11. Interact! Discussion and collaboration can be the
    quickest way to significance and its fun

38
Proposed Topics

• Overview of projects
• Future directions for the lab
• Strategies for success at the bench
• When to submit
• Nitty-gritty of running an academic lab

39
Why publish at all?

• Its what we do - disseminate knowledge
• Practical considerations
• Career demands
• Grad student
• Post-doc
• Faculty member
• National Academy
• Nobel Prize
• Funding
• Getting it
• Keeping it

40
When to submit?

• What is your primary goal - numbers or impact?
• Numbers (as soon as possible and sooner than you
  think)
• Impact (intrinsic, external validation)
• Do I have a story? The story I wanted to
  tell? (think in terms of figures, outlines)
• To what extent is it original? Timely?
  Significant? What would take it to the next
  level?
• Do you have competition?
• How do you determine these things?
• (Read, interact, submit)
• The risks of being too early or too late
• Remember, it almost never accepted without
  revision

41
Proposed Topics

• Overview of projects
• Future directions for the lab
• Strategies for success at the bench
• When to submit
• Nitty-gritty of running an academic lab

42
Nitty Gritty

• What are the expectations of and the support
  from your Department?
• Does it vary greatly from Dept. to Dept.?
• What does start-up funding cover?
• How much money in support do you need to fund X
  number of people working for you?
• How do indirect costs figure into your budget
  requests?
• What goes into the other sections of the R01
  besides the research plan?