We study how a eukaryotic cell inherits an exact copy of the entire genome from its mother during cell division. The process is simple enough to describe: every time a cell divide, it should send one copy of each its chromosomes to each daughter. Executing this process is an entirely different matter. Depending on the species, there can be as few as three chromosomes (e.g. fission yeast) or as many as hundreds (some butterfly species and hyperploid plant species). Every cell division must account for each and every chromosome, making sure that there are no mistakes. In the context of the cell division, 'genome inheritance' means 'chromosome segregation' or physically moving one copy of each chromosome into each of the daughter cell. So how does the cell ensure accurate genome inheritance? What biophysical processes move the chromosomes during cell division? How does the dividing cell 'know' that its daughters will receive one copy of each chromosome after cell division? How accurate is chromosome segregation really? These are the questions that generally interest members of the Joglekar lab.
Answers to many of these questions are known with varying degrees of detail. For instance, decades of research shows that the job of moving chromosomes is the responsibility of the kinetochore. The kinetochore is a macromolecular machine that generates mechanical force to move each chromosome. One specific area of interest in the lab is to understand the biophysical nature of this force generation process. How do kinetochore proteins generate force to move chromosomes? How is this process regulated? The second topic is even more interesting. The cell 'knows' if something is wrong with chromosome movement, and it can halt cell division until the mistake is corrected. The signals that the cell uses to arrest the progress of cell division are known as the 'Spindle Assembly Checkpoint'. But how the cell knows that there is a mistake is a bit of a mystery. We are working hard on understanding the sensing mechanisms embedded in the kinetochore that are responsible for triggering the spindle assembly checkpoint.
Genome Inheritance during cell division is a fundamental process in cell biology. It shapes evolution, and it is critical for the well-being of any dividing cell or organism, including humans. Defective chromosome segregation plays a role many diseases includingcancer. It is also implicated in age-related infertility. In the short term, we want to understand the mechanochemistry of genome inheritance, and how it may go wrong. In the long term, we want to re-engineer the whole system from scratch. We want to build artificial kinetochores that function just as well or even better under certain conditions that the native kinetochores.