Time for a giant leap

It’s that time again when I have to take an important decision – choosing my thesis advisor/lab. Its funny that each time I have to make an important decision, I feel like I just cannot afford to make a wrong choice here. Though in the past, I have made some wrong choices at times, I could work my way through them and it never felt like all things would come to an end. However, choosing an advisor is a totally different issue on all levels. If I went wrong here, things could be brutal and all that I had to do to come this far could just come crashing down.

The more I think about it, the more I realize that this is one decision which will decide so many other things in my career in science. This is my 3^rd and last rotation and though I am glad I was able to eliminate one of the three pretty easily, choosing between the two remaining still seems a daunting task. These days almost every day ends with me adding more and more things in the pros and cons lists in my head and thinking so hard to the extent that I’m really drained out of energy. However, it did give me a good chance to think about what are the things that I really need - to be able to do some good and important science.

Freedom – I join a lab, I pick a problem a statement that I find really interesting and try to answer it in the best way possible. I realized it’s very important for me that I am the person designing my research with my advisor and not have somebody else do it for me where I just end up doing what someone else proposed. It should be like my story, my very first story in science :)

Support – More than half the things you do tend to not work in biology. Then begins the troubleshooting and I should mention that though the joy of discovering what went wrong and fixing it and getting working assays is truly satisfying, it does take time to nail down the culprit. It is this time when you probably need the most support from your peers in the lab and your advisor – when things refuse to work. You need people who could throw at you many more possibilities why the assay is not working and through all this, your advisor giving you a helping hand.

People – I have come to believe that it’s a huge resource to have a set of motivated people around you to bounce ideas off. I’ve been a part of several labs in the past and I’ve seen lab meetings where people just listen to the speaker’s work, ask a few questions and leave and meetings where the others in the lab actually make a good effort to see how the speaker’s project can be made better – what would be another cool thing that can be done at this point, what would that one big idea be to claim your hypothesis convincingly. The synergy is amazing – everybody trying to make each other’s project better and better. Oh well, I am glad I was able to sample such labs as well.

There could be several other things that someone else in my stage could come up with but I figured to me the most important things would be the freedom and the support; maybe I could compromise for the 3^rd factor but definitely not the first two. Another few weeks and I’d have this choice made. And that would mark my first success in grad school :)

Blogger glitches

What do you do when you realize that one of your recent posts that did have comments shows 0 comments? What do you do when you notice that one of your posts is missing and better still, what do you do when you realize all your blog posts have disappeared.

I’ve experienced the first scenario and (fingers crossed) hopefully will not see the other cases in my blog. Based on whatever little research I did following this event, turns out Blogger always had such issues and the blogger help forum is inundated with such queries which happen on a regular basis. I wouldn’t be too surprised if this is the case with platforms other than blogger as well.

That reminds me – sometime in February the gmail blog had a post about a gmail issue where 0.02% of gmail users found their gmail empty when logged in. I was completely taken aback reading this and 0.02% is quite a bit given the large number of gmail users. I’m sure none of us can imagine something like that happen to our accounts – can clearly see how crazy it would drive us given that we depend on it so much; the moment you log out of it, you want to log back.

Now coming back to the current issue about content on blog disappearing. It is reported that this could happen when the user tries to change the url, export it to another domain and other things that I don’t completely understand. In my case, no changes were done at all. Though it was frustrating in the beginning, I’ve decided to have a copy of all the posts that I put up and will put up. After all, you don’t want to spend time and energy to do something you really like and see it vanish into thin air someday unable to retrieve it from anywhere.

For all the bloggers out there – I am prepared to deal with this if it happens again and at a larger magnitude. Are you? It’s time you are.

Data analysis – the good and the bad

Last 2 weeks in April were crazy for me with finals and term paper submissions and assignments and trying to wind up experiments. As far as research was concerned (my 2^nd rotation in an awesome lab), I was able to stick to the plan I made - did all the experiments that I had to and was left with data analysis in the last few days. Yes, the other side of things. Getting experiments to work is just the first half of the story; trying to make (any) sense of the data you get out of experiments is the other half.

It was only after I plunged into this other half, did I realize how much of data I generated that it felt close to impossible to analyse all of it before my big day – when I’d be presenting in the lab meeting. I was beginning to wonder which is the tougher one that makes you go crazy – the experiments or the data analysis. It really tires you out. Though I got through everything and even got some interesting results, I still don’t have an answer to that question (which I think is a profound one).

But I did learn a couple of things about this whole process of studying data. The most important thing being - never leave this task to the end. Never. The best way to go about it is to start getting a hang of how the data looks as and when you have some of it ready. In my case, each time I did an experiment I took a good number of movies so I could have a good number of data points but once I started analysing the movies, I realized that they were not enough. I needed so many more movies. This happens when you are studying motors in invitro assays (which was what I was studying). There were also some data sets where I felt I’d be better off with a longer movie, maybe slower/faster frame rate and such things. Its always good to know what are the things you need to work on before you do the experiment again at a later point.

Another important aspect – honesty. Since I sort of knew what kind of a trend or pattern I should see in the parameters that I was studying across several different experiments, each time I got to a point where I was able to compare these cases, my mind would try to work its way and make sure I was seeing exactly the expected trend. I found it slightly hard in the beginning to do a completely unbiased analysis. But I got around this by telling myself that what people have seen in the past need not be true at all and maybe I’d see something novel (well, I know this is not true in most cases but you get what I mean, atleast it motivated me to do a blindfold analysis). Its very important to be completely honest with yourself and be able to communicate to others how exactly you went about analysing your data. That way me giving a talk in the lab meeting was good – I realized each person has a different style of looking at his/her data and even representing it. I think that’s one of the things that has to be given a good thought – what is the one best way to represent your data that will definitely make people think and not just listen.

All said, I’m glad I learnt these small things early on. Also, just so you know my talk went very well and the rotation was extremely satisfying :)

PS: About the title - I don't think there's an ugly side to data analysis, is there?

‘Live and learn’: H.M

Ever wondered how scientists came to show that hippocampus in the brain plays an important role in the formation of memories. The best way to show this with 100% confidence is probably do some studies on a person who has his hippocampus removed, right. H.M was one such person who took the field by storm. He’s probably one of the most famous neuroscience patients and has been invaluable to the advancement of the field.

When he was about 27 years old (1953), he underwent an operation to get rid of his frequent seizures. Though the seizures reduced, the operation changed his life completely as he had a memory loss and could not form new memories as well. He couldn’t remember who he spoke to that morning or what he had for lunch that day. During that time it was widely believed that the ability to form memories and retain them was a function that was distributed all over the brain. Through several studies on H.M, Dr. Scoville and Dr. Milner could show that memory can be distinct from other cognitive abilities.

I recently got a chance to attend a seminar by Dr. Suzanne Corkin from MIT who was once a student of Dr. Milner. Corkin (and her lab) studied him for four decades until his death in 2008. I didn’t even know that a person H.M existed until my friend told me about this talk.

Corkin and her students gave several tests to H.M over all the years that they studied him and were able to learn an insurmountable amount about the brain and learning and memory. She told us about how declarative memory could be episodic (event based) or semantic (fact based). Citing her examples – recollecting your dinner time last night would be episodic, you know the capital of France being Paris as a fact but you probably don’t remember when was the first time you ever came to know of it, that’s semantic. Turned out that though H.M had no episodic memory he was still ok with semantic – he could tell things about WWII, which country the US was fighting, so on and so forth. This is just one example and several such interesting things were deduced by experimenting with H.M. After his death, MRI scans of his brain were taken and his brain has been sliced and is now at UCSD.

It was an engaging seminar and at the same time overwhelming that one person who contributed so much to the field (who probably didn’t even know how phenomenal this was for the field) is now no more. Corkin mentioned she is writing a book on H.M and said he was like a family member to her and her lab. She said he was a person with a good sense of humor and he used to say ‘you should live and learn; I’m, living and you’re learning’. When I later asked Corkin about the emotional bonding between them, she said ‘we did as much as we could but that can’t replace what he lost. We celebrated Christmas together and he thought I was his friend from high school’.

Given how closely she worked with H.M and got to know him, I think her book will be a page turner – both scientifically and otherwise. Looking forward to it.

The Essence of Shape

As kids we all learn that various cell types have different shapes and sizes. But how many times have you actually thought a little bit more about it. I think the very first time I thought of this aspect was when we were explained in undergrad what happens in sickle cell anaemia – red blood cells are crescent shaped rather than disc like and hence deliver lower oxygen levels to tissues. And after that it was only during my senior year and now in grad school that I am beginning to grasp the complexity involved in this concept called shape and how vital it is.

Cell division is a fundamental process in which cell shape plays a huge role – imagine how complex a task it actually is for the cell to calculate the location of its central plane (if the division is symmetric of course) and be able to divide into two. I got a chance to read this interesting paper published in Cell this February that came out of the Chang lab at Columbia University. They put sea urchin eggs in microfabricated chambers of different shapes with volume of each being the same as that of the egg. In ways I don’t completely understand the egg now takes up this shape of the chamber – rectangle, ellipse and triangle. They then saw the plane of division in each of these cases and observed the positioning of the nucleus which ultimately is the deciding factor for how a cell divides. They show by experiments and by a very elegant mathematical model that the microtubules ‘sense’ this cell geometry and orient the nucleus along the axis of cell division accordingly by exerting forces on it.

If that didn’t make any sense at all, how about this – a protein X in some organism Y localizes to only to membranes that are convex; all it needs is this geometric cue rather than some cell specific cues. Yes, this was shown to be the case for a spore forming protein in bacteria by Richard Losick’s group at Harvard, published in Science sometime back. They purified the protein and when incubated with different kinds of vesicles in vitro, the protein localized to the smallest vesicle, which is the most convex one.

That’s cool stuff out there.

Getting through the first hitch

I’m just finishing up my 2^nd rotation and would begin the 3^rd very soon. Following that, I’d have to decide a lab and then at some point decide what my thesis would be on – my research for the next few years of my life.

In contrast to the European system, I think for most students (definitely for someone like me as I was not sure what exactly I wanted to work on) rotation is a very good way to decide what kind of work you like and also if you fit in a particular lab, so on and so forth. Halfway through this rotation, I think I have an idea of what I want to study and also beginning to get a hang of what kind of lab culture do I fit into.

Once you figure out these things and join a lab, the next big thing would be picking up a problem to work on. Though I haven’t been there yet, it is a good thing to know where the field you’re interested in is right now and what are the questions you can ask and also answer them. This reminded me of an article I read a year back that Uri Alon wrote – How to choose a good problem. For all those considering research and just about to begin to narrow down what you really like, this is a great resource. Ultimately, you do want to do what you truly enjoy but this gives an insight into things that you’re probably not thinking of right now. To give you a flavour look at this picture he draws. I think it is a really well thought out one and only a person with a lot of insight and who’s been there, done that can come up with something like this.

Pretty pictures, pretty movies

Where else can you get to see beautiful images and movies other than in biology?

Here’s an image of cytoskeleton that you can just keep staring at:

Red – actin filaments, Green – Microtubules, Blue – nuclei

These filamentous structures (microtubules and actin) are not complete without a set of proteins called motor proteins. These proteins are great transporters in cells. Simply put, they pick up the cargo that has to be transported, hitch hike on these filaments and deliver the cargo to their destinations. And why do we need such a well developed mechanism – One good reason is the need for speed. The cytoplasm is a viscoelastic material and if stuff were to be moved within the cell from one end to the other just by random diffusion and no directed motion at all (as we see on these tracks), one can imagine how inefficient that would be.

Here’s one of my first movies (yay!) that I took in this current lab that I’m rotating. Its kinesin moving on Microtubules. Microtubules have a + end and a – end and the kinesin that I am studying moves towards the + end. Its easy to see which is the + end of the microtubule as you see bright spots of concentrated kinesins at these ends.