One of those moments

One of the moments that I remember, as a graduate student, very vividly is the time I burst into Joel's office. The past few months had been exciting since I had discovered an inhibitor. We were now doing a key experiment: Will the inhibitor kill cancer cells? I gathered the results in my hand and burst into Joel's office, with a big smile on my face and asked him whether he wanted to know the results. That moment kind of justified all the nights I stayed up purifying protein. It also justified taking the wrong tube out of the refrigerator and discovering an inhibitor instead.
Today I saw the same smile on Reshma's face...

Okay, let me back track a little bit.

A cell is made of nucleus and cytoplasm at the very gross level. Nucleus is where the DNA resides and cytoplasm is where things other than DNA live. Every event within the cell is regulated and if the regulation goes kaput, the cell too goes kaput. It might not necessarily lead to cancer but every human disease can be tracked down to some protein within the cell becoming dysfunctional. So the regulation of proteins, so that they do what they are supposed to do only at the time they are supposed, is important.

I work with a protein which hydrolyzes ATP in presence of DNA, the energy currency in the cell. When ATP breaks down it releases energy which my protein is supposed to use to do something. I do not know what it does-that is what a big part of my research is.

Now, the protein is a highly active. Give it DNA and ATP, it will happily break down the ATP within matter of minutes. In fact so much so that if it was left unregulated it would just consume all the ATP and kill the cell for the cell cannot survive without ATP. As Tom Thompson, the ex-chairperson of my department at UVa, asked at my viva: "How the heck is the protein regulated?"

Truthfully, I never even was looking at it. I assumed, just as Joel, my advisor, assumed, it is all a matter of availability of the correct DNA.

Anyway, at one point we decided we are going to look where the protein was present in the cell. Was it in the nucleus (which we confidentially assumed it would be) or in the cytoplasm?

To cut a long story short, what we ended up finding is that the protein normally resides in the cytoplasm. So under normal conditions it never even sees DNA, therefore, it does not hydrolyze ATP. But give the cells a little bit of stress that damages the DNA, the protein moves into nucleus.

We did not believe we would see it. I still cannot believe what I saw under the microscope.

But it was one of the moments...