Posted in Articles: Thursday, November 17, 2011
I joined Claudio Aguilar’s lab here at Purdue University. He has two different systems that he works on simultaneously: cell biology with yeast and cell biology with mammals. So basically, yeast is a very good system to work with as almost all the proteins in yeast are conserved in the mammalian cells. For example, different discoveries that have been made with yeast are applicable to mammalian cells as well. It is so easy to work with, easy and fast to get all the data, so I like to work with the yeast system.
My research is focusing on a protein (Epsin) that is important for endocytosis, and we see how that protein is absolutely required for the cells to survive. So the interesting thing is, the endocytic function of the protein is not required for its survival. So there’s something else going on. The story starts when Claudio figured out exactly what’s going on – why the cell’s need that particular protein to survive.
I followed up with Dr. Aguilar’s work and the interesting thing I found is that there is a region in the protein that is made up similar kinds of amino acids – proteins are made up of amino acids - and this region of the protein has the same consecutive amino acids for a stretch. The reason this is important is because in several neuro-degenerative disorders like Huntington’s Disease, this stretch of amino acids expands and makes the protein pathogen. So it’s not the same protein. Huntington’s Disease has a different protein that undergoes its own expansion. This amino acid is called glutamine and the process is polyglutamine expansion. What it seems is that this poly-glutamine region is important for certain functions of the protein to help it maintain viability, proper cell division and so on.
The reason this is very important is because when people try to understand polyglutamine mediated neuro-degenerative disorders they usually look at the expanded protein, but nobody has ever looked at why the small stretches are there in the first place. That is what we are trying to do. We are using this protein to understand the physiological relevance of the small polyglutamine stretch that is there in the first place and then probably move on from there and see, when it undergoes expansion, what changes: if there’s any gain of function, loss of function and so on.
Yeast cells are a diverse population, so even when something is wrong with them, you need to look at thousands of cells to be sure that it is really going on, because even in normal cells you will find one cell out of, say, 5000, in which something is wrong – but that is not really relevant. So in order to do this, we need to look at these thousands of cells and then look at their perimeter outline, and conduct image analysis. We have to do this manually and it takes a lot of time. We feel that if there were an automated approach to the image analysis, then we could do it much faster.
Information Theory methods and tools could really help us we think. And, such as analysis would be not only faster, but since we’re currently doing the image analysis manually, there might be some information that we’re missing. An automated system of image analysis would not miss these critical pieces of information. So bridging information theory with cell biology and the resulting image analysis would be become more information-rich and we would potentially get a lot more relevant information from an automated system.
I also realize there is one more thing in which image analysis automation could help us with. Epsin is made up of a large number of amino acids. We know only about 10% of what a whole sequence does, of what the individual amino acids do. Perhaps by looking at different sequences of different proteins we might be able to understand more about what each amino acid or what each group of amino acid is responsible for and so on. Basically what this shows is that if you have a lot of epsin, it promotes cells to become cancers. We feel that bridging information theory with cell biology is necessary in order for the science to progress at this point.\"