How to start a "grant club"

Starting a lab is sometimes a lonely pursuit. You are now in charge of everything and must have the final say on papers and grants that go out. While it may have been like this even before your transition, now your grants do not benefit from the shelter of your mentor's name and the success of your new lab depends on them.

Finding good readers becomes really important, because you need people who may not fully understand your field to take a serious look to your proposal and give you feedback. The more detailed and honest it is, the better. While senior investigators with experience in obtaining NIH funding will help, sometimes they have time only for a passing look and you are still wondering whether there is something you should change. Since there are eight of us who were hired in the past few years, we organized and started a monthly "grant club", where someone submits their latest effort for slaughter. R01 aims or full proposals, foundation grants or career award applications are sent out to everyone and dissected over pizza and beers. After 6 months everyone seems to really like it, in particular the fact that we all provide a lovingly brutal sounding board to test ideas. Now we started adopting stragglers from other departments, who have an interest in neuroscience.

The recipe is simple, 1) make a Doodle and find a day when most people can come, 2) the host/grant writer sends out their draft a few days before, 3) the host gets pizza/beer or fancier fare and other people can chip in (Girls, if I guy is hosting, remember the fruit and cookies...), 4) to break the ice you can ask for advice on how to get students or can just start complaining about things you would like to change in your institution, 5) discuss the grant. Do the aims weave a good story? Is the questions asked approaching a fundamental mechanism? Can you even tell what the fundamental mechanism studied is?   Is it too much work? Too little work? Is it cohesive? If Aim 1 doesn't work, will everything fall apart? and so forth and so on. Be nice and honest, but more importantly try and be helpful.

Which brings me to a sticky issue, be mindful of the purpose of these meetings to find the right mix of colleagues. As far as I can tell, we all really care about each other's success and we all enjoy discussing each other's science. Many of us don't have a chance to talk apart from this monthly occasion and it is great to bring everyone together. You may already have a wonderful group of colleagues that have offices right next to yours and that you meet often for coffee. Or you are in a small place where there are only a couple new hires or in a big place where everyone is competing and spying on everybody else. Then I would say, propose an online grant club with friends at other universities or meet with people at other local institutions. It makes such an enormous difference to have a cohort to lean on and if you have no grants coming up, meet anyways to talk about science, lab management or
which grants people have applied to.

Biotium GelRed and GelGreen to replace ethidium bromide

We would like to run agarose gels without ethidium bromide to avoid the need of dealing with toxic waste and to reduce the use of dangerous chemicals in the lab. We talked to quite a few vendors about this and started trying things out.

We started with AMRESCO EZ-Vision dyes which are SYBR Green based and were not very happy with them. Staining was very weak and we could not reliably image the gels on our existing UV image acquisition system without a SYBR filter. We had no intention of buying a new image acquisition system just for this so we kept looking. 500uL $89.52 from VWR

We tried Promega Diamond Nucleic Acid dye was also pretty weak and it is not an in-gel stain, so requires additional time for post-staining. We decided to keep looking. 500ul $70.00 from Promega

Finally, we started having good results with Biotium GelRed. GelRed is very sensitive and looks orange/red on the UV transilluminator like EtBr. GelGreen was not quite as bright, so we focused on GelRed, but optimization was needed. We had two primary issues: 1) bands which are very close to each other appear like they are fused together and the molecular weight marker was just a smear, 2) bands sometimes ran at a different weight than expected.
Since one of our genotyping PCRs needs to distinguish between a 400 and 480bp band it was very important to get good separation. Biotium recommended to reduce the amount of dye in the gel or to try post-staining because both the separation issue and the run length issue could be due to the larger size of the Biotium dye which can impair DNA motility. We lowered the amount of in-gel stain from 10,000X to 40,000X and it still worked pretty well, but a range of 20-30,000X may work best (around 2ul for a 50mL gel). Another way to improve separation is to post-stain if necessary and post-staining is relatively quick (15-20 mins) and does not require destaining. In addition the post-staining dye can be reused saving some extra money. Because of the size of the dye, agarose concentration is also critical and concentrations above 1% are not recommended. 500ul $104.42 from VWR

All in all for regular genotyping PCR which is most of what we do the GelRed works very well and while it's somewhat more expensive than the other dyes, it is a substantial difference in sensitivity. In the end the decision comes to whether you want to have an EtBr free gel bench and how much money you are going to spend for the more expensive dye.
5g of EtBr ($64.20) will make 1L of 10,000X solution (final concentration 5mg/mL), while 1L of GelRed at 30,000X would cost $35,000. Yet, 1L of stock will make 100,000 100mL gels: if you run 10 100mL gels a week or around 500 gels a year, you'll spend $0.32 in EtBr or $417.68 in GelRed. I would be interested in finding out how much you spend yearly for EtBr disposal.

When is my grant getting reviewed?

Have you ever tried to google when a study section meets or when to expect an answer back?  While this is easy to find out for the NIH, it's not necessarily that straightforward for foundations. So as a followup to my list of grants, I thought I'd have a ongoing post with a list of timelines. If you have any additional timeline info for other grants, let me know in a comment and I'll update the post.

NIH grants (see here for full list):

Submission: R01 1st cycle Feb 5 - 2nd cycle Jun 5 - 3rd cycle Oct 5
K99 1st cycle Feb 12 - 2nd cycle Jun 12 - 3rd cycle Oct 12
Renewals, resubmission are a month after first submission
Review: 1st cycle Jun-Jul - 2nd cycle Oct-Nov - 3rd cycle Feb-Mar
Scores: 2-3 days after review
Comments: 2 weeks after review
Decision (council meeting): 1st cycle Aug or Oct - 2nd cycle Jan - 3rd cycle May
Award: 1st cycle Sept*-Dec - 2nd cycle Apr - 3rd cycle Jul
Notes: * Funny things happen in September at the NIH because of the end of the fiscal year, so be mindful of possible Sept awards. I've heard both of grants being pushed through quickly or being delayed or cut.

Simulated resubmission scenario. FAST (13 months): R01 first submission Feb 5/close but not fundable scores back Jul 15/resubmission Jul 5/good score Nov 2/council approval Jan 15/money comes Apr 1
SLOW (17 months): R01 first submission Feb 5/close but not fundable scores back Jul 15/resubmission Nov 5/good score Mar 4/council approval May 20/money comes Jul 1

Muscular Dystrophy Association research grants:
http://www.charitynavigator.org/index.cfm?bay=search.summary&orgid=4134#.UqfGtxZ5nzI
MDA will resume RFAs in the Fall 2014: http://mda.org/research2/grant-types

LOI submission: Fall cycle Jun 15 - Spring cycle Dec 15
LOI response: 1-3 days after submission (this is very fast and you only have 4 weeks left)
Submission: Fall cycle Jul 15 - Spring cycle Jan 15
Review: Fall cycle October - Spring cycle April
Scores/Decision: Fall cycle Nov/Dec - Spring cycle May/June
Award: Fall cycle Feb 1 - Spring cycle Aug 1 (8 months after LOI)
Notes: 11/2013 - grants below 90% score rejected, top 10% pending Board Meeting decision on funding pay-line
3/2014 - Feb 1 2014 grants funded starting May 1

March of Dimes general research grants:
http://www.charitynavigator.org/index.cfm?bay=search.summary&orgid=4045#.UqfGRRZ5nzI

LOI submission: April 30 (check current RFA)
LOI response: by Jul 15
Submission: Sept 15
Review: February/March
Scores/decision 2014: rejections end of March, acceptance April/May (can be as late as mid May)
Award: Jun 1 (13 months after LOI)
Notes: 8/2013 - following LOI acceptance 22% funding rate

NARSAD Young Investigator Grants:
http://www.charitynavigator.org/index.cfm?bay=search.summary&orgid=4153#.UxE-RRbfbzI

Submission: in February (keep checking in January for the Call for Applications to come out, in 2014 it was February 19th)
Review: ?
Scores/Decision: August (2014 award decisions starting Aug 7 and rolling)
Award: January 15th (11 months after applications)

The New PI hits the 6th month slump: how do you keep proactive?

Caspar David Friedrich - Der Monch am Meer (detail)

I have been quiet for a while because I did not know what to say. Six months ago, the day before I started my new job I was full of excitement (here), but now I barely feel I can keep my head above water. It is somewhat impossible to describe the tsunami that hits you when you start running a lab: 1) the navigation of a completely new administrations with its quirks and habits, 2) ordering, including choosing things, getting quotes, keeping track of orders, generating relationships with vendors, 3) hiring new people, 4) training new people, sometimes multiple new people at the same time, 5) managing renovations, animal rooms, animal protocols and orders, 6) reconciling budgets, 7) writing papers, 8) writing grants, 9) developing new relationships with colleagues and collaborators, and last but not least 10) deciding where the lab must go and where to place your bets on your future and on the future of everyone you hired. You are hit from every corner, every day with some kind of issue or emergency and because everything is new to you, every decision has to be pondered. Some days I literally feel like I cannot breathe.

The lab is somewhat moving, grinding away slowly, finding a rhythm between having everything we need to get things going and doing experiments. A couple of proposals are out and papers are still lagging. I am exhausted most of the time: most days I have no time to read or write or even think and get home late at night in a stupor. I try to continue to do busy work on the laptop as I watch TV, but not much gets done. I started taking vitamin B and drinking caffeine again to get me going in the morning. It's the 6th month slump: when you still remember how things were moving at a steady clip before and you feel completely enveloped in molasses. It is also vital to keep moving because things need to get done and you can see that sooner or later you will get there. But you are questioning everything.

You do not want to talk to people because they will think you are weak and not worthy, so you weather the bad days and rest a little on the good days. Then you talk to your peers and everyone is going through this or has experienced it at some point. Someone warned you at the beginning that the first year was going to be tough. In light of all this I decided to share because it's not just you, reader, or me, it's growing pains for a lot of people.

In the midst of all this, I opened my iPad after 6 months and discovered that way back then I had bought "The Seven Habits of Highly Effective People"by Steven Covey and I started from Habit 1: Be Proactive. I liked that Covey brought up the serenity prayer from 12-step programs "Grant me the serenity to accept the things I cannot change, courage to change the things I can, and wisdom to know the difference". The adrenaline roller coaster of jumping from "crisis" to "crisis" always reminds me of an addiction-inducing paradigm, but that may just be the neuroscientist in me. Fight-or-flight, reward, fight-or-flight, reward. The trick here is to break the vicious cycle and to prioritize, but also to know which battles to take on and focus on those. You hear the words "time management" thrown at you endlessly in your first year, but being proactive is different. It's identifying the things that are important and that you can change (either in yourself or in others) and purposefully act on those. This also require to get out of your shell and to talk to a lot of different people to better understand your field, your institution and your new role. There may be things you didn't know you could change and people you didn't know had the power to change them. There may be things that you truly cannot change or control and you have to find your way around them or don't let them get to you. I'm practicing and we'll see how it goes....

What do you have to do to get noticed?

A friend forwarded a recent Harvard Business Review article about why incompetent men get promoted and competent women remain unnoticed, which has been doing the rounds this week. The argument is that men display enough arrogance and bravado to get the to the top by the sheer force of their charm and self-promotion, until they are found out to be incompetent....leaving many competent and qualified women in the rubble because women do not display similar behaviors. Though this may ring true sometimes, there are multiple layers to discuss and I recommend a great blog post from Athene Donald, a physicist in Cambridge and women's champion.

What struck me more than anything in the article is trying to figure out what you need to do to get noticed in your field. Through the years I have had numerous conversations with friends and colleagues on how to best "spin stories" for papers and grant proposals. How much of a claim are you willing to make based on the data you have to increase the appeal of your work? How do you promote yourself and get invited to meetings and seminars? What is the best attitude? There are people who are well recognized in their field and very well published and funded, yet there is chatter at meetings on how their work is derivative, how they jump from cool project to cool project without really getting to the bottom of anything and how their talks are all hot air and overblown hypotheses. Yet, if you strive to do transformative science and fail a lot in the process, but 50% of what you produce is true, is that enough?

And then there are the rare people who are humble and shrewdly present their work simply. "We think this could be interesting, what do you think?" and the talks they give just blow your mind with how amazing the data is. But, these are the minority. Maybe because they are so brilliant, they don't need the puffed out feather and peacock tail in full display.

Nowadays, sadly or maybe just like everything else, your success in science depends on self-promotion. You have to give talks and then be invited to give more talks where you have to explain to a wide audience why what you do is cool. In your grants you have to rope people who may know very little about what you do into choosing you above other hundreds of applicants and giving you money. Even in hiring people you have to present you new lab in a light that will make it appealing for a top applicant to come work for you. The purists hate this and complain to no end about how your science should speak for itself. But to be fair the level of specialization is such that maybe 4-5 people in the world will really intimately understand what you do and these often will not be reviewers for your grants and papers.

It is a constant struggle in my mind on when to shake those back feathers and fan that tail. Do I tout my own horn at every little accomplishment in my department? Should I remind people who invited me for talks in passing that I was invited? Do I walk up to important people at meetings and just introduce myself pitching my "awesome" research? How much can I comfortably spin a story to make it more appealing still feeling that I am true to the findings?

Is it a female thing? After all female peacocks don't need that tail, they have other priorities. But while it may be more common in women to be humble and matter-of-fact, I'm not sure this is just a gender issue. It's more your natural inclination and your training, since as a scientist you must trust in the data above all. This is going to be a very interesting learning experience about human nature more than anything. Meeting season is starting soon, so I better start getting ready.

Photo credit:  Jebulon (Own work) via Wikimedia Commons

Why we like Quartzy for ordering, inventory and reagent organization

Starting a lab means that you get to establish culture and workflow, which I have previously discussed here, and one of the main problems I have encountered in the past is the lack of a proper inventory and common reagents constantly running out stopping experiments dead in their tracks. If you are in a large lab, you can obviate to this problem by having your own private stock of everything that is vital to your research, but I am starting a new lab which is small, and I want sharing and good labmanship to be a strong feature of my group.

I was on LabLife for a few years and I was never really into it because nobody else in the lab used it, and now that it has transitioned from a free version to the paid version, LabGuru, paying for it is out of the question. It costs $10/month per person and I am not willing to pay the much for every postdoc, student and undergrad to have access to inventory.

We have a Dropbox folder where I keep all the protocols and we share data, and I'm looking into getting server space for more data storage. But now that we ORDER A LOT to get the lab set-up, I also need a place where every order, quote and part number is recorded and where we can write down where everything is. My postdoc lab has recently established a Google spreadsheet for orders with a template that everyone can access to enter what they need. Everyone can then go check when the order has been placed and whether it has been delivered. This is easy and free, but again it's a one trick pony.

So, after seeing all the little fliers for Quartzy, we decided to give it a try and absolutely love it!!
Starting with the Orders tab anyone in the lab can put in an order and when the system is integrated with a particular vendor's catalog the order is auto-populated with all kinds of useful information. Then the order is submitted to the approver (i.e. me or a lab manager) who orders stuff and marks it as Ordered. I think in some institutions you can order directly via Quartzy, we are not allowed to do that and mostly have to use iBuy. When stuff comes whoever unpacks it marks it Delivered and has the option to indicate where the items are now located AND automatically everything that was delivered ends up in Inventory. Yay! Handy searches and item categories (Equipment, Antibody, etc) make finding stuff in the inventory very easy and the view for each category is fully customizable so that the most important info is easily available, like serial number for equipment vs epitope for antibodies. There is a tab for Protocols and one for Facilities and while I don't use the Protocols because ours are in the Dropbox, I already set up the sign-up sheets for our large equipment and I'm excited to use the scheduling function.

While entering everything at the beginning is very time consuming, I'm hoping this will pay back in the future. We recorded all the special prices and quotes we received as a new lab and if something is running low the person noticing this will just have to click Reorder. If someone is wondering where stuff is, they just have to look it up in the Inventory. In addition, if you have many freezer boxes of samples and reagents and you record the exact location of every tube, you can generate a box map and a list, which saved us from having to get FileMaker or equivalent database software.

Finally, the customer service is absolutely wonderful. The chat box on the right allows you to IM a customer service rep on the spot. I had an issue with the ordering layout because there was no easy way to keep track of the ordered and delivered dates. While the rep could not help me right then and there, she told me they were working on it and two days later the layout changed to give you a much better overview of what is going on. I'm really excited to see how Quartzy changes in the future and I would urge everyone who uses the site to give lots of feedback so that it can become even more user friendly. Now, I just hope they don't go the LabLife way and charge an arm and a leg for it.....

NIH to implement Individual Development Plan (IDP) requirement

Just got a note from the NIH Office for Extramural research that the NIH released a notice (NOT-OD-13-093) promoting the implementation of Individual Development Plans (IDPs) for all grad students and postdoc on any type of NIH funding. Each institution will have to devise their own strategy to develop and monitor IDPs and they must also be introduced in the Progress Report.

There is constant talk of IDPs at career development workshops and Science Careers developed a website last year where you can develop your own (myidp.sciencecareers.org), which I discussed in detail in a previous blog post. Briefly, an IDP is an actionable plan which can have short and long term goals for career advancement and professional improvement. Bottom line, I think this is a great idea, because it would promote more accountability in mentoring, as mentors must be involved in monitoring the IDP of people on their grants, but the decision on what templates to use and what kind of reporting to do will make all the difference. IDP structure vary widely and the fact that institutions are left to their own devices in deciding which IDP to use may mean a completely different approach in different research centers. Some universities already have IDP templates and others don't even know what an IDP is. The Science Careers site is a good introduction and it is more detailed than many university templates (here and here), but the workflow for developing goals is a little clumsy and it should be better if this wants to become a major point of reference for IDP development.

While a lot of "mentoring" done for NIH grants ends up remaining only on paper, I have experienced on my own skin how establishing mentoring teams and mentoring plans will eventually get you a good portion of the mentoring you need. Even if you get one tenth of the mentoring described in your mentoring plan, you are already way ahead of the curve and more official emphasis on reporting mentoring will definitely improve the odds. I assume that now that my K99 award has transitioned to the independent phase, the R00, I will have to use an IDP for students that may end up as personnel on the grant.

Learning how to hire #2: Advice about hiring new lab members

I just went through the month-long process of hiring a first research assistant for my new lab. If navigating the posting of a position through HR was tough, what followed was even tougher. Partially thanks to Craigslist (see here), we ended up with almost 200 applications in 4 days, got them down to 10 viable candidates for phone interviews and 6 candidates for in person visits. This decision also involved dozens of phone calls to references and a lot of thinking about defining the responsibilities of the position and the required experience and how much training should be involved. Overall, it was very informative and we are really happy with our selection.

I tried to follow some of the advice I had received in the past from senior investigators (here and here) about taking my time and being mindful of my "gut feeling", but a recent series on LinkedIn from Joel Peterson, the chairman of Jet Blue, has a lot of great insight on the 10 biggest hiring mistakes.

Mistake #1: Hiring yourself. Diversity is good to bring balance to the workplace. You just want to make sure that all personalities gel together. You also cannot expect that everyone will be just like you and have to accept individual differences.

Mistake #2: Hiring too fast. Take your time hiring and finding the right person for the job. This has been repeated to me many many times by countless people. Do not rush to fill your empty lab or you will risk hemorrhaging cash and not being able to start on your best foot.

Mistake #3: Hiring the resume, not the person. Someone may look great on paper, but may not fit the culture or the energy of your lab. The first few people are incredibly important in defining the way you want your workplace to feel: vibrant and exciting? fun and relaxed? focused and ambitious? Peterson puts in terms of "brain and heart", you want someone smart and motivated, but also someone passionate about the job at hand. One more post I wrote about establishing your lab culture here.

Mistake #4: Interviewing on autopilot. Do not just go through candidates all in a row without a strategy.  I interviewed 8 people on the phone in one day and by the end of it I was completely exhausted. Because HR asked me to be consistent, I developed a script for what I was going to say about the position and for the questions I was going to ask and I took notes on all the answers, and that was my saving grace because by the end it all blended together. I took notes on qualifications, but also "gut feeling" on whether the person would be a good fit. The in-person visits were split in several different days so that we really had the time to talk to the candidates and better explore insight or inconsistencies coming from the previous chat.

Mistake #5: Lazy reference checking. Always always check multiple references ON THE PHONE and ask difficult questions if necessary. This may be by far one of the most important things. Firing people is difficult and emotional, but for some reason firing people in the lab seems sometimes impossible and is always messy. I have seen a lot of horrible situations where the fit was just not right and where information may have emerged from candidly talking to the references. During my own recent hiring, I received tons of honest feedback positive and negative which greatly informed my hiring decision.

Mistake #6: Freezing out your team. The entire team should be involved in the decision process and I may add, people should have power to veto a hiring decision. For a large (40 person) lab, my postdoc lab had an amazing combination of people who for the most part got along well, which is very rare for such a group. One of the most important features of the hiring process was that we all participated in it and talked to candidates, took them out for lunch and got to know them a bit. Everybody's opinion was considered and that was very important in making sure that only great people got in.

Mistake #7: Only hiring inside or outside. By definition in science you almost always hire from outside because people cycle through as they rise through the academic ranks. Moving around is favored and people are discouraged from remaining in their PhD lab for a postdoc. But continuity has its benefits and there are positions that may require more continuity and better knowledge of your institution.

Mistake #8. Blowing the first 90 days. This is another very important one! The way someone interacts with the team and absorbs the lab culture is dictated during their onboarding process. The culture you want them to absorb and the techniques you want them to master will become the focus of the training period and the way your new hire performs may depend on this.

Mistake #9. Focusing on money. If you wanted a high-paying job, you wouldn't be in academic science, but the lesson here is to provide rewards and positive feedback that go beyond compensation. In his great book about motivation, Drive, Dan Pink discusses Autonomy, Mastery and Purpose as important driving forces in employee motivation. See my post here for using these forces in the lab.

Mistake #10. Not firing a bad hire. Firing often seems impossible for scientists and a lot of "lab horror stories" revolve around people who should have been fired years ago (or not hired in the first place). I am not looking forward to this and I really hope it never happens, but it is so much easier for all parties involved to end things quickly and ease a transition to a different position.

Hope this is helpful. I will definitely try my best to avoid these mistakes.

A new paradigm for autism therapy from cancer research

I do not have much time to read for pleasure, but before a long flight I finally managed to pick up a copy of The Emperor of All Maladies, Siddartha Mukherjee's Pulitzer-prize winning "biography of cancer". The book is masterfully written and absolutely mesmerizing, but it is not my goal to review it here, as more poignant reviews were penned 3 years ago when it was first published.

As a scientist one of the most fascinating things is to follow the process of discovery: see what physicians and scientists inferred from what they saw and how they came to often very wrong conclusions with the very best intentions, how ideas became fixed in the common knowledge and how revolutionary approaches came to be. Like the organisms and molecules it studies, medical science is constantly evolving and ways for looking at scientific problems with new eyes are always necessary.

One thing that struck me of the evolution of the thinking about cancer, is the fact that at first we did not know that the same name encompasses multiple different disorders and the common approach was to find a cure-all drug that would work on everyone. After much often devastating trial and error, we now known specific drug regimens may only work on a specific form of cancer. Cancer is in fact becoming the poster-child for personalized medicine, an approach requiring a specific understanding of the individual patient's and tumor's history and genetic makeup. The rationale is that each type of cancer and maybe each individual cancer is different and the hope is that once we figure out what makes each tumor explode in millions of proliferating cells, we may be able to design a tailored regimen to stop it.

Reading about those initial struggles on how to deal with a very heterogeneous disorder that yet often looks similar in many patients, made me thing about the changing concept of autism nowadays. The herculean genetic efforts of the past few years have determined that autism is not caused by common genetic changes, but it is more likely due to a single faulty gene in each case. The rub is that the mutated gene could be one of dozens or hundreds, and as many clinicians and parents may tell you, each affected child may need to be considered as a unique presentation of the disease. This confusion is reflected in the recent changes to diagnostic criteria listed in the latest version of the Diagnostic and Statistical Manual of Mental Disorders or DSM-5, which groups all autistic-like symptoms of different severity under the term Autism Spectrum Disorders (ASD). So, is it one big disease or hundreds of different ones that we cannot diagnose individually? Is there a miracle drug which will work on everyone in the spectrum or do we need to figure out a way to group patients with defects in similar molecular processes, or even treat everyone differently?

Some food for thought came from the recent demise of arbaclofen, an experimental drug for autistic behavior in individuals affected by Fragile X Syndrome. Fragile X Syndrome is a common cause of intellectual disability and is often associated with autistic features, but as in all forms of ASD the symptoms and the behavioral problems are greatly variable. As described in a New York Times article last month, arbaclofen was deemed a failure after it showed no affect on a phase 3 clinical trial and funding was pulled. Yet a small number of patients showed remarkable improvement in their social interactions and parents are desperate that they will now lose access to the drug. It is possible that arbaclofen may only be effective in a specific subset of cases and that other patients may need different drugs. It is also possible that the children who responded well to arbaclofen may have improved on their own or responded to anything, but we will never know if we do not test these conflicting hypotheses. If there is a "type" of autism that responds well to a specific drug, it may possible to discover more types and their treatment, as is being done for cancer.

Learning how to hire #1: Find your Research Assistant on Craigslist

I need to hire a Research Assistant either with a very specific attitude or set of skills, so I wrote a somewhat detailed job description and hoped for the best. But where to get access to a lot of applicants? My postdoc lab had recently hired an RA, advertised on Craigslist and got 90 applications, but since I was not involved in that hiring and I do not have a big HHMI lab, I was somewhat skeptical of how many people would apply to my lab.

At the same time just advertising on the Jobs listings of my institution may not be enough to reach a wide audience. I perused biotech/science job listings on Craigslist and when I saw that the Library of Congress advertises there I was sold. The listings are sparse, but that may not be a bad thing and there were not any recent academic RA jobs posted. The listing cost $25 which is a pittance compared to what postdoc listings cost on professional organization websites.

Lo and behold I posted the job on Friday afternoon at 5pm and I had more than 100 applications in 3 days with peaks on Monday morning of one application every 20 minutes. After discarding applications from candidates with no experience or qualifications in other fields, I had a pool of a few dozen people who looked interesting. Then, after combing through another 50+ applications from HR, I had multiple candidates with some combination of the required set of skills and experience. We had so many applications we had to shut down the listings after 4 days because going through them all would become unmanageable. Interestingly, the two applicant pools were almost completely separate as only a few people applied through both systems, so Craigslist was great for diversification. In both cases I had more and less experienced applicants and a similar distribution of ages. And now the phone interviews begin...as far as I'm concerned, the Craigslist experiment was a success.

Never pay retail....in the lab

I am an avid shopper and I love nice things, but as a grad student and postdoc I didn't have much
money, so I've become an expert on where to find the best bargain and how to wait for the things I wanted until I could get the most favorable price. I doubt it's safe to buy lab supplies on eBay (though there are quite a few things available), but in a few months of running a lab I discovered that the "never pay retail" rule is also true for labs.

Every new principal investigator (PI) knows about the new lab discounts you can get from multiple companies, but what I didn't know is that you should never be satisfied with those and that you can get discounts all the time....for almost everything. You just need to ask, and better you need to come armed with quotes from multiple companies and from pricing that was extended to other PIs. I have quite a few friends that have started labs in the past couple of years plus multiple people at my new institution, so I've been collecting quotes and deals from everyone. Then I can go to the different vendors and get quotes and pit them against each other and against the best prices I have heard of. This is time consuming and it is sometimes uncomfortable since you may develop a rapport with certain vendors and you may be genuinely torn between different products, but the dance is worth your time. If a company offers 30% off and you like another product better, you should ask the competing company to extend the same discount. Everything is ridiculously expensive and your start-up money is very precious.

Some things I've learned:
- If you are in the market for a good microscope and have found one you like, ask whether demos are available. Demo microscopes are just lightly used and you can get a better price for what you want or some free bells and whistles which could become handy.

- Always see if you can get free reagents/consumables with your equipment purchase and if you get a $1000 ask for a quote for what you need with the new lab discount and get even more stuff for free.

- Find out if your institution allows you to purchase your fridges and freezer for a regular stores. Best Buy will have freezer for a fraction of the price of big distributors like VWR or Fisher and you can find deli case fridges from restaurant supply stores at half to a third of the price. Google "2 door beverage merchandisers" and you'll see.

- The price of chemicals may vary wildly and one friend recommended to always double check since she level of purity does not necessarily make something more expensive. Companies will make the most requested item the cheapest, so you may be able to get a better purity for a smaller price tag.

- Always always ask for a better discount....and always ask around for what your friends and colleagues are doing. What was the norm in your old lab could be done with alternative approaches that are much cheaper and there may be other things you want to splurge on.

Every little bit counts.

Self-sabotage in academia: tips on what not to do

A friend recently posted a great article from The Chronicle of Higher Education on "Self-Sabotage in the Academic Career", which points out 15 ways you can hurt your career during the tenure process. The article is applicable to any tenure-track position whether in science or the humanities and you should just read it. While asking for advice from senior investigators in the past few months, I had already received some of these tips (here and here), but it's worth keep repeating them, since they come up over and over again.

These are the ways to be self-destructive:

In your field:
You don't seek out multiple mentors.
You don't seek out external evaluations.
You aren't well known outside your institution.

In your institution:

You pay too much attention to personal relationships - or too little.
You fail to understand the cultural norms of your institution.
You have been involved in one too many departmental squabbles.
You are too selfish or too selfless.

In your research:
You are either perfectionist or perfunctory in putting your work into print.
You hold on to revisions too long or rush them out.
You lack resilience in the face of failure.
You got stuck in your dissertation paradigm.
You collaborate too much with colleagues from graduate school or your postdoctoral years.
You fail to have a coherent research plan.
You haven't figured out who you are.
You are guilty of any kind of academic dishonesty.

In summary, innovation, independence and collegiality are things to strive toward while identifying as many mentors as possible to help you through.

A spectrum of mental health disorders

I have written a lot of about management and grants and lab equipment, but I have not written much about science. I was trying to keep the blog consistent, but the nature of the internet is not linear: readers come in and leave at any point on anything their web browser selected for them. I usually talk about science with colleagues and friends, but it may also make sense to repost some interesting findings or discussion points.

An issue very close to my heart is the study of mental illness, which is what I do. A few weeks ago I was discussing autism with a foundation and I was asked whether I believe that autism is a mental illness. I found it an odd question. "Of course autism is a mental illness" I replied "it is diagnosed according to the DSM, the Diagnostic and Statistical Manual of Mental Disorders. What else is it supposed to be?" Clinically, by definition autism is a mental illness because it is a change in brain function which severely disrupts behavior and life, and it is a psychiatric disorder. It is a disorder, like many other disorders of other parts of the body, but mental illness still carries a different kind of stigma it shouldn't carry (which could be a discussion to have in another post).

I was looking at a recent editorial on the journal Nature, Mental health: On the spectrum, which  discusses the imminent publication of the new edition of the DSM, the DSM-5, and talks about what is a mental illness and how different disorders relate to each other. The piece describes how the diagnosis of psychiatric disorders in the past 60 years has changed and on how research has modified the way medicine approaches the problem. It also proposes that multiple mental disorders from intellectual disability to OCD, may lie on a continuum, a clinical spectrum without the clear boundaries defined by the diagnostic textbooks. I am a strong proponent of the spectrum view, but clinically you want to group cases that look the same together so that you can draw some conclusions. Yet, the genetics of mental disorders has shown that reality is much more complicated. The editorial is a very good read and food for thought.

Qiagen Finder 45-pathway Cignal array: the good, the bad and the ugly

I am still not sure whether this is going to be a good review or a bad review. It may shake out one way or another as I write it.

We do a lot of signaling as we work on a intracellular signaling scaffold which functions in a lot of different pathways, so I always pay attention to new email from SABiosciences/Qiagen on their new PCR and luciferase arrays. Upon reading about it the Cignal Finder 45-pathway array seemed to provide an awesome way to apply very sensitive luciferase assays to test 45 pathways in a single shot.
It is a 96 well plate with 45 reporters in duplicates and 3 positive and negative controls that you can use to test you drug, siRNA, over expression plasmid on your cell line of choice. The protocol is simple and straightforward: the DNA is in the wells, you add the cells and transfection reagent and the next day you test for luciferase and renilla activity. At $1,600 for a 10 plate pack, plus dual-luciferase assay reagents, it can run around $200-300 per plate, which in triplicates for 2 conditions can be almost $2,000 per experiment. But screening 45-pathways at once could be totally worth it and SABiosciences always run some kind of deal on the plates (and you can use a fraction of the luciferase reagent recommended in the Promega protocol).

We know our protein of interest would really strongly activate NF-kappaB and we have done it with a different reporter, so that was our positive control. The first plate was amazing! There were very clear difference between reporters, the duplicates looked very consistent and a whole bunch of interesting pathways lit up in addition to NF-kappaB in our experimental condition. The dynamic range of response was incredible with some reporters with intensity in the 2,000,000 intensity units and some in the 2,000. And so we embarked in a huge study with over expression and siRNA...and ordered another 10-pack. Qiagen provided us with a handy Excel file for analysis where we just needed to plug the results of luciferase and renilla for each plate and everything would be calculated and plotted for us.

I was intrigued by some of the results and started paying a lot of attention to the intensity measurements, and that is when things started getting ugly. We had noticed that some of the duplicates were asymmetric in intensity when a low intensity reporter was next to a very high intensity one. I had had similar problems in the past with white plates in our luminometer, where we noticed spillover of fluorescence in neighboring wells. Some people say it's the fluorescence passing trough the white walls, others that the detector is far from the plate and the fluorescence spills over from above like a halo. Also instead of looking at the results in the Qiagen spreadsheet where they are in linear format, I analyzed everything in plate format, where I could see which well was above, below, left and right of any particular reporter. That is when half of our hits became uninterpretable because they could simply be due to spillover from the strong hit next door. Qiagen recommended to half the amount of lysate, but that didn't help much as the results were basically identical. So we were stuck with the option of spending $500 per troubleshooting attempt or find some other solution....

They said it must be our luminometer, which is a possibility, but that's the machine we have in the department and their product should work even for older machines. They gave us 2 plates for free for testing, which was nice, but still leaves for $500 per troubleshooting for each one of the other variables (machine, reagents, lysate amount). Right now I am faced with a conundrum: I have some data I believe from the array and some data I do not believe, which I think is due to spillover. I cannot publish the whole array because I would have to explain it is a problematic product and I have requested for a sample of the 6-8 reporters that are iffy, but I was told I had to buy them individually, which I am not inclined to do at this time, since I do not want to waste my grant money to troubleshoot their product for them.

At the same time, their reporters work beautifully and the data we have is very robust, though for us it was more a 30-pathway array than a 45-pathway because of the issues.....I am open to suggestions from other people who may have tried the product and who may have other ideas. Also, I am not entirely satisfied with the way they recommend to analyze the reporters and I'd love input on that also.

Advance planning: the benefits of the 0, 18 or 60 month plans

As I start the lab I am trying to figure out where things are going to go in the future and come up with a career development plan. The information on career planning out there is varied and I picked a few suggestions I like.

A 60-month plan. I have been reading a great blog called The Professor Is In, which is run by a former college professor turned career advisor for younger academics. Even if you do not hire her for her services, the blog is great and it covers everything from career planning to what to wear for an interview to how to network. The Professor firmly supports a need for a 5-year plan, nicely structured month by month in an Excel spreadsheet where you identify all the deadlines you are planning to meet. This is not your run of the mill 5-year plan where you daydream about where you want to be in 5 years, this is a place where you can write down grant deadlines, conference deadlines, paper deadlines for years in advance and foresee what you are going to do March 15th two years from now. I am a compulsive planner and list maker, so the 5-year plan spreadsheet was very appealing to me. Grant deadlines are similar from year to year and conferences are planned years in advance, so after a few Google searches I had a nice detailed plan for the first 5 years of the lab. While I think this is great, since it forced me to look for a lot of grant sources and integrate my current plan for publications with grant deadlines, none of this may ever happen, as the plan keeps changing on me, so in the framework of a 5-year plan shorter plans may be in order.

An 18-month plan. I just finished reading Sheryl Sandberg's book Lean In. I have been a long-term Sandberg's fan and followed some of her advice, but this is another story for another post. In Lean In she proposes an 18-month plan, which is not as short as 1 year, but not as daunting as 2 years. The goal is to set an 18-month deadline for improvement or career development: you can either want to develop a skill, enter a new field, set a deadline for funding or publication of a particular project, develop a course. In her formulation, this is not as detailed as having a monthly spreadsheet, but it could also be used as a shorter version of the 5-year plan by planning actual deadlines for only one and a half year at a time, while keeping in mind longer terms obligations, such as when you are supposed to teach for a semester or when you are going up for tenure.

A 0 to 6-month plan. Finally there is who says that planning is futile, that your research will change completely and that your deadlines will fluctuate. I have heard from a few friends that within a year of starting your lab, your goals may have changes completely because the science took unexpected turns, and all the detailed experiment you had planned are not happening. Writing a particular grant may be postponed and other interesting deadlined may come up randomly following a friend's suggestion. Maybe a shorter 3-6 month plan is more realistic and you need to just think in the shorter term to hit specific deadlines without feeling the overwhelming weight of the future. Somewhat like being on a diet where losing 5 lbs in the short term is much less daunting than setting out to lose 30 lbs.

All three options have their pros and cons. I respond well to detailed long-term planning, but at the same time, I am very flexible when the plans do not go the way I planned. Someone who gets discouraged if plans are not kept, may find detailed long-term planning depressing and may prefer the 3-6 month timeline. Overall, I think a combination of the three may be possible with a detailed 6-month plan, a looser but definitive 18-month plan and general broad stroke plan between month 19 and 60. Maybe it's time to revise my 5-year plan spreadsheet and see how it goes.