December 4, 2017
Meet Ishan Deshpande
In September, Ishan Deshpande defended his PhD thesis on how Mec1-Ddc2, a tumor suppressor involved in DNA damage response, assembles at sites of DNA damage. He is one of the few PhD students who pursued a PhD thesis in one of the FMI facilities and was supervised both by Heinz Gut from the Protein Structure Facility and Susan Gasser.
During your PhD thesis, you gained new insights into molecular processes at sites of DNA damage. What fascinates you with this topic?
Ishan: Every day each cell in our body faces approximately 100,000 DNA damage insults. This is quite remarkable! Intriguingly, DNA damage comes in different flavors such as base damage, single-strand and double-strand breaks. Such DNA damage events may cause mutations and chromosomal rearrangements. Obviously, this does not bode well for the stability of our genomes and indeed DNA damage forms the basis of several diseases including cancer. Our cells respond to DNA damage quite efficiently by employing around 450 proteins and several redundant pathways. How these proteins form an intricate network of processes to maintain genome integrity is what fascinates me.
You did your PhD thesis in the Protein Structure Facility and in Susan Gasser’s lab? Why this arrangement?
Ishan: There is definitely a growing need of collaborative science. To answer difficult questions many scientists are now working at the interface of different disciplines and sharing their expertise. I think this brings in unique perspectives and strategies to answer scientific questions.
I am fortunate to have experienced such a fruitful collaboration during my PhD. Our question was “How is the Mec1 kinase assembled and activated on DNA damage sites at the right place and at the right time?” Using the structural biology expertise in Heinz Gut’s lab, we were able to solve several crystal structures to build a model of Mec1 assembly at DNA damage, whereas, using the DNA damage expertise in Susan Gasser’s lab, we could show that proper Mec1 assembly is important, especially after damage by UV light in the S phase of the cell cycle. Only by combining the knowledge derived from these two approaches, were we able to gain a better understanding of Mec1 assembly and activity.
What were the biggest challenges in your project and what helped you overcome them?
Ishan: For me, one of the biggest challenges was to master and effectively use two different techniques: Structural biology and yeast genetics. Also being a part of two labs, Heinz Gut and Susan Gasser, was overwhelming in the beginning. However, I am very happy that I was given the opportunity to be a part of this inter-disciplinary collaboration.
Several people helped me overcome this. My immediate mentors, Heinz Gut and Jeremy Keusch, provided great support and advice. Susan Gasser is a strong advocate of collaborative science and leads by example. Kenji Shimada introduced me to the world of yeast genetics and is a patient teacher.
Your time at the FMI is slowly coming to the end. What will you take with you from the FMI as you pursue your scientific career?
Ishan: I thoroughly enjoyed my 5 years at the FMI. I was closely mentored by Heinz, an excellent structural biologist, and Jeremy, an expert biochemist and molecular biologist. I am sure I will benefit from this structural biology and biochemistry training.
What was important to you as you looked for your next position as a postdoctoral researcher?
Ishan: I think it is important to diversify. My postdoc research will be in a different area of research and I will be using techniques that I have not used before. This might be challenging initially, but will be a great opportunity to expand my research horizon. It is also important to know the people you would be working with and check if you are compatible with their work culture. I am lucky that I quickly found a lab that could provide me with all of this. Additionally, I will be moving to a different continent. So, I cannot be more excited about my next position.
Deshpande I, Seeber A, Shimada K, Keusch JJ, Gut H, Gasser SM. (2017) Structural basis of Mec1-Ddc2-RPA assembly and activation on single-stranded DNA at sites of damage. Mol Cell [Epub ahead of print]