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?

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

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

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

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

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

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

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

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

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

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

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

37. Strategies for Success at the Bench Find a question that genuinely excites you Know and invest in yourself, learn how you learn best Experimental design: Simple, simple, simple, but not too simple Do controlled experiments (Ahhhhhhhhhhh!!!!!!!!!!!!!!!!!!!!!!) Design your experiment with the end in mind Fail fast, so you can succeed Regarding new techniques, be fearless but not stupid A year in the lab can save a week in the library Apply principles of good time-management: budget your time, be disciplined, work hard but take breaks too Efficient with things, effective with people 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?