Lab Meeting 2010 I am aiming for something in between.

Lab Meeting 2010 I am aiming for something in between

Past Years 2002 - When do I begin writing? 2003 - How do I manage time effectively? 2004 - Principles of responding to critiques of your manuscript or grant 2005 - (1) Overview of the lab’s projects (2) Future directions for the lab (3) Strategies for success at the bench (4) When to submit your manuscript (5) How to run a lab 2006 - (1) How do you do good science? (2) How do you manage time effectively? (3) Are there specific strategies that promote scientific success? 2007 - (1) What are the differences between working in industry and academia (2) What makes a good mentor (3) How do you write a scientific paper 2008 - Lab speak feedback #2-4 (Global lab strategy, etc…) 2009 - Lab speak feedback #5-7 (Scientific funding, publication..)

This year’s marching orders What is the near- and long-term plan for the lab. How do you formulate a plan for the lab? Philosophy of mentoring? How to review a manuscript? Time management - general comments Is multitasking necessary to be successful? Does it even work? How do you fail fast?

Steve, do you have a 1-2-5 year plan? Did you have a scientific plan when you started? Did you want to study HD, Arc, etc when you started? "don't put all your eggs in one basket" - did you choose to work on different things on political purpose (grants from different sources)?

Steve, do you have a 1-2-5 year plan? See global lab strategy discussion to follow Did you have a scientific plan when you started? Yes. When you start a lab, you should have a ~1-5 year R01 type plan and a long-term plan Did you want to study HD, Arc, etc when you started? See global lab strategy discussion to follow "don't put all your eggs in one basket" - did you choose to work on different things on political purpose (grants from different sources)? Absoluteley not

Does the Term “Global Strategy” Fit? ENTJ = Field Marshall - apparently, strategic thinking is my specialty What does “Global Strategy” mean? An all- encompassing strategy? Top-down command and control management? Cogs in a machine? Where do creativity, serendipity, and independence fit in? Is lab science an endeavor that is well-suited to the development of a global strategy? Is constructing a “Global Strategy” the best strategy? What are our goals? What is our philosophy?

What are our goals? 1. To creatively elucidate novel mechanisms of plasticity and neurodegeneration. 2. To do whatever it takes, including the invention and development of new technology, to achieve #1. 3. To develop lab members into outstanding and increasingly independent scientists. These “Global” goals have remained unchanged since the lab was established in 1999!

Why these goals? 1.Because I find these two research areas fundamentally interesting, and I continue to believe we have contributions we can make in both areas. 2.I find having one focus to be too narrow and more than two, too much. I like that we have two sides to our lab. It prevents “group think” and creates wonderful opportunities for collaboration and cross fertilization (which itself helps us accomplish these goals). 3.I deeply believe that science should be creative and inventive. The development of new technologies and approaches is fun and solves several problems at once. Note: (1) Not political; (2) Not even practical per se

How do we achieve them? 1. To creatively elucidate novel mechanisms of plasticity and neurodegeneration. - Above all, recruit the smartest and most creative people that are available - Pursue interesting novel ambitious science questions - Create an attractive environment in which to train - Care for and mentor members - Avoid jerks - Develop an armamentarium of diverse approaches - Publish in the best places whenever possible - Match people’s passions with their projects - Encourage people to explore their interests and give them freedom to pursue them within reason - Encourage and support fearlessness and creativity - Develop rotation projects jointly - Read widely - Foster collaboration within the lab and outside the lab - Fill the lab with people who would be good collaborators - Be good collaborators to those who interact with us

How do we achieve them? 2. To do whatever it takes, including the invention and development of new technology, to achieve #1. - Encourage new lab members to develop a new technology that is appropriate for their project and fits with long-term lab goals - Steve - Automated microscopy - Montse - Survival analysis - Sean - DHA - Carol - Y2H - Punita - High throughput screening - Andrey - Photoswitching - Erica - Tap tagging/proteomics - Ian - Stereotaxic injection/lentivirus - Hong Joo, Carol, Montse, etc… - whole animal work - Maya - e-physiology - Collaborate to share risk - Crystallography - Weisgraber - Software and microscope development - Nikon, Media Cy, Fidelity Foundation

How do we achieve them? 3. To develop lab members into outstanding and increasingly independent scientists - Above all, recruit the smartest and most creative people that are available - Pick and pursue interesting novel ambitious science questions - Create an attractive environment in which to train - Care for and mentor members - Be cognizant of strengths, weaknesses, and career goals - Avoid temptation to be overly controlling - Allow trainees to struggle - Provide opportunities and support - To speak - To write - To get funded - To network - Find the resources needed for their success - Develop an armamentarium of diverse approaches - Publish in the best places whenever possible - Match people’s passions with their projects - Encourage people to explore their interests and give them freedom to pursue them within reason

How do these goals translate into specific projects? 1.Does it involve mechanisms of plasticity or neurodegeneration or the development of relevant technology? 2.My level of interest: Am I passionate about it? Is there a compelling big picture question or the possibility of a result that would shift paradigms (or are we mopping up details that others can do equally well)? - The invention of automated microscopy and survival analysis - The concept of coping responses in neurodegeneration - Protein conformatics 3.Historical: Have we made discoveries in the past that lead directly to this project? Are we developing a body of knowledge (concept of CV)? Do we have a competitive edge? - Activity induces Arc transcription -> Discovery of response elements in Arc -> Search for a zeste-like factor - mAb 3B5H10 -> Xtalography + automated microscopy -> search for toxic species, toxic complexes, therapeutic applications 4.Novelty: Are we pursuing something that we have discovered or created or are we doing “me too” science? - Novel discovery of PKD association with the NMDAR-> novel PKD signaling system to control AMPAR trafficking and gene expression -> PKD & plasticity in vivo - Arc -> WAVE3 in the nervous system -> dendritic and spine plasticity 5.Funding

Other factors? 1.Does each trainee have a project that is sufficiently independent that they have something that they can call their own? 2.Are there connections between projects that could be a source of collaboration, interaction, and support for the person leading the project and other lab members? 3.Is the trainee too focused or spread too thin? 4.Are we developing projects in such a way that pieces can be taken out of the lab and used as seeds for people to start their own labs? 5.Are we managing risk effectively? Do projects have a plan for a “home run” as well as “base hits” 6.Are we continuously re-inventing ourselves or are we using the same approaches? Are we planting the seeds today that will allow us to be at the cutting edge and relevant in the future?

So are you saying we have no goals or plans? The big picture goals/plans remain constant. The specifics change over time depending on people’s interests, opportunity, and resources.

Does that approach to goal-setting accomplish anything? Long-range goals made in 2005 Develop an imaging tool to do cellular “systems” biology Build a microscope with a spectral detector Develop programs capable of fully automated analysis Develop new probes that uniquely harness the technology Move in vivo Discover a new pathway for synaptic plasticity Develop stereotaxic injection and lentivirus methods Develop in vivo approaches Make new transgenic lines (tap-tag; proteomics) Make a new knockout line Become familiar with behavioral approaches Develop the capability of performing RNAi screens in primary neurons (and get funding to do it!) Establish chemical genetics approaches in the laboratory

I don’t find it to be a very useful concept I prefer to think in terms of specific goals and ways to optimally balance and achieve them Successfully meeting both our research and training goals can require complex, multifaceted strategies Long-range strategic thinking and initiatives should occur in parallel to keep us positioned to do science that is relevant and significant

I'm sure you've gotten plenty of ideas. But in your annul talk, I was wondering if you could elaborate on your philosophy of mentoring scientists. On one extreme, a PI can be a maniacal micromanager and on the other extreme he/she can be completely laissez-faire. I know you've mentioned that by letting students "sink or swim" they learn to do science now as opposed to delaying the inherently hard process to a latter time. But students often need guidance and accountability. How do you strike this balance? Does your approach differ between graduate students and post-docs, or from one student to the next? This question goes hand in hand with the balance of lab personnel. Do you make sure that there is a pool of experienced post-docs and grad students to mentor younger students, and how important is it that these experienced students are knowledgeable in the core research areas of the lab?

What makes a good mentor? Surprisingly controversial Two extreme views: Sink or swim v. “Mother” What is your view of training? Are people a means to an end or an end themselves? Can it be learned? Mentor - in ancient Greek mythology, Mentor was the teacher and guide of Telemachus, son of Odysseus. Mentor was actually Athena (the Goddess of Wisdom) in disguise.

What makes a good mentor? Caring Empathy (What is your E.Q.?) Accessibility Generosity / unselfishness Appreciating individuality Acting on principle consistently The need to develop; role of patience & independence Honesty / integrity Savvy: tactical and strategic thinking Adapted partly from HHMI / BW Handbook, Nature’s guide for mentors, my own experience

What makes a good mentor? (what I have learned trying) Recognize your limits. Some things you can fix, some you can not. Make the most of what they have. People aren’t Legos. Prepare for disappointment. Appreciate the unexpected result (what others might call failure). Ask your mentee what they think they need. There is nothing new under the sun. Benefit from those around you. Enthusiasm in the mentor is essential but motivation (in science) in the mentee has to come from within.

My Role My goal: To help you find your passion, teach you necessary skills to complete your goals, and to foster your independence toward your chosen career My commitment: (1)Access: (2)Advice: strategy, tactics, writing, etc… (3)Freedom: to succeed & fail regularly; to make one big mistake against my wishes but nothing leading to embryonic lethality (4)Resources: financial support, environment, etc… (5)Career-long support (‘til death do us part) My expectation: 100% commitment or please find another lab/career

Tailored Mentoring 1.Career goals? What does it take to get you from where you are to where you want to go? 2.What are your strengths and weaknesses? 3.Blind spots? What do I (or others) observe? 1.Organization 2.Communication - writing, speaking 3.Competence 4.Self-discipline 4.Have things changed since the original plan was formulated? 1.Personal problems 2.Academia -> industry -> academia

What is the best composition of a lab? Survey of Nobel Laureates (% Grad students): 0%-85% “Students are more open to taking on projects that make a major impact in science and spend longer in the lab. Post-docs are often too focused on getting out and getting a job to tackle an important problem. Students are also more dynamic and plastic, less stuck in their ways.” - An MIT Laureate

What is the best composition of a lab? Other advice: A Harvard colleague - “If you start a lab at a place like Harvard or UCSF, build it with graduate students. The students you can recruit from those places will be way better than the post-docs you can recruit.” A UCSF colleague - “About 3 years ago, I reviewed my career and realized that most of the major advances from my laboratory were made by students. Since then, I got on the admissions committee and have tried to increase the proportion of students in my lab.”

What is the best composition of a lab? Students Dynamic, plastic, intelligent, ambitious Inexperienced, time-consuming, less stable Post-docs Productive, focused, can be experienced, bring new approaches Can be competitive, overly narrow, stubborn, risky PositivesNegatives

Finkbeiner Lab (1999-2010)

Experience and Post-doc Recruitment What do we mean by experience? Techniques, mileage, scientific judgment? Do the most exciting applicants have the experience that we are talking about? How can we tell? Can we recruit post-docs with particular experience? Should we? Our Most/least productive? Grad student or post-doc?

Finkbeiner Lab (1999-2010)

How do we achieve them? 1. To creatively elucidate novel mechanisms of plasticity and neurodegeneration. - Above all, recruit the smartest and most creative people that are available - Pursue interesting novel ambitious science questions - Create an attractive environment in which to train - Care for and mentor members - Avoid jerks - Develop an armamentarium of diverse approaches - Publish in the best places whenever possible - Match people’s passions with their projects - Encourage people to explore their interests and give them freedom to pursue them within reason - Encourage and support fearlessness and creativity - Develop rotation projects jointly - Read widely - Foster collaboration within the lab and outside the lab - Fill the lab with people who would be good collaborators - Be good collaborators to those who interact with us

How to review a manuscript. I found a few papers on approaches/expectations that people have when they review a paper. I am curious to know your thoughts and how you approach a review of a manuscript. Also I think it could be useful to highlight mistakes that junior reviews (eg post docs and graduate students) tend to make. Thanks Gaia

Why Review Papers? Advance knowledge by keeping the literature pristine - if its in your field, you will be stuck with it! It is your duty to the scientific community It inevitably makes you a more effective scientist Foster relationships with editors

How to Review Papers Be disciplined and skeptical (Where’s Waldo) Are the data believable? Are the conclusions supported? Does it all add up? What is missing? Why? Separate major and minor issues in your review Is it important/novel?

Rookie Mistakes Trust what you read too much Too much focus on technical details Too long No distinction between major and minor concerns Lack confidence to declare something unbelievable Specific recommendations about publishability in the review

Sami Time management

Measures of Success Productivity = Papers (Quality, Quantity) Time Presentations & networks are important but productivity is the commonest measure Critical for getting a job, getting resources for a project (i.e., fellowships, grants) Productivity in science can be frustratingly non- linear and weakly related to hard work Productivity often grows as training progresses

Time Management How do you do you balance personal life and outside goals with science? As far as I can tell, it never gets easier No magic Be pro-active Decide what you want your life to be about Set tangible goals (annual, monthly, weekly) Organize your time to maximize your effectiveness Budget your time, determining how much time to devote and which activities you decline

Time Management Moving beyond the checklist Enhancing relationships and accomplishing results rather than focusing on things and time Efficient with things & effective with people I. Crises, deadlines II. Prevention, PC, Planning, Recreation III. Interruptions, some mtgs., popular stuff IV. Trivia, busy work, time wasters UrgentNot Urgent Important Not Important I. Stress, burnout, putting out fires II. Vision, balance, achievement, fewer crises III. Ineffectiveness

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

As we all become busier and busier, and perhaps as wireless internet has become ubiquitous, multitasking has become more and more common. Sometimes we do it because we feel like we're getting more accomplished, and other times because there's a world cup game that we really want to keep an eye on during lab meeting. :) Anyhow, my question is to what degree has multitasking become a necessary skill to be a successful academic scientist/PI? At what level of multitasking does the quality of any one particular piece of work suffer? How do you figure out a balance where you can increase your productivity but not shortchange the other thing(s) you're focusing on? Ian

Multitasking What can I say that is useful and not obvious? What is it? Probably does not mean doing multiple thinking tasks simultaneously

Pseudo-multitasking: My Experience Origami Diverse tasks concurrently, if not simultaneously When you cook (or do experiments), can you get things to finish on time without burning them? Do you need silence to work or do you need music to keep your mind from wandering? Swim suits and overpasses

Pseudo-multitasking: My Experience Regularly rotate my effort between projects (30-60 min blocks) 1.To keep from getting board 2.To benefit from crock pot thinking 3.To make progress on projects that I can’t stand 4.As a mechanism to generate regular feedback for those waiting for it a.Improves the learning experience of those who are waiting for it b.Manages the emotional expectations of my collaborators

Hi Steve, You probably already have plenty of good topics for your lab meeting and I am not sure if there is much else you could say on this topic besides what you've mentioned in the past. But if you're still looking for topics, I would like it if you could expand a bit on your approach/strategy to "failing fast." For example, how do you decide when you've "failed" and should move on to the next thing. Obviously, there is a fair bit of frustration that comes with making something work and I realize that it is a judgment call. I am just curious how you personally make that judgment call. Thanks, Hengameh

Failing Fast - Pursuing high risk / high reward science effectively Critical risk management strategy The wrong way The right way: Determine the reward Is it possible? What is it worth? Determine the risk(s) What is (are) the critical POC results that would enable me to believe the project is worth the investment Attach a deadline to achieve each of the POC results and stick with it: NO-GO -> Next idea

Slumps DiagnosisTreatment Everyone has them! 1. Technical problems 2. Technical issues OK but no interesting results - Are you spread too thin? - Are you too focused? - None of the above 1. Simplify, be systematic, read, take a different approach, talk (or better, do it) with people who have it working 2. Varies - Focus more - Consider adding a project - Commiserate, endure, and recreate or abandon the project

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