Our researchers are a fierce driving force behind therapeutic development and future treatment. Let’s find out what makes them so passionate about KIF1A! Each month, one of our invested members of the KIF1A Research Network will be in the spotlight. Dr. Ajay Chitnis is next in the line up for our monthly Q&A.
Ajay Chitnis, MBBS, PhDSenior Investigator and Head of Section on Neural Developmental Dynamics at National Institutes of Health, Division of Intramural Research
Dr. Ajay Chitnis, MBBS, PhD and his team at the National Institutes of Health (NICHD) investigate the mechanistic analyses of the neural deficits in KIF1A Associated Neurological Disorder (KAND) pathology. In collaboration with Katie Drerup, PhD (NIH), Chitnis and Drerup labs are developing and analyzing a zebrafish model of this genetic disorder, using specific dominant de novo mutations in the motor domain of KIF1A. Using live imaging of cargo localization and transport and whole brain analyses of neural structure, they aim to define the cellular and anatomical changes that occur in a zebrafish model of KAND. The expectation is that characterization of cellular and neural systems level deficits in the zebrafish model of this disease will provide a foundation for development of potential therapeutic approaches.
If you could have any superpower, what would it be and why?
Ha Ha, that is a surprisingly difficult question. I considered various superpowers that could help me solve world problems, along the lines of what you might find in the Marvel Universe, but that felt disingenuous. What came to mind instead is something that is not really a “superpower”, something that many people already have but that has always seemed out of reach to me: to be able to make beautiful music. Making music puts you in a sublime state of mind and at the same time, you lift people’s spirits and move them with a unique universal language. It’s a superpower I would enjoy if I had it!
When did you know you wanted to be a scientist? Why were you drawn to this field?
I was ten when Neil Armstrong took his first steps on the moon. Following the Apollo program first drew me into the wonder of space and the stars. As I went through school, I learnt from Physics why the sky is blue and how we get rainbows, Chemistry taught me about the “Lego” blocks of the universe and the rules by which they recombine to make all that was around me. Science opened the door to the magic of the universe at all scales! I came to Biology much later, first hooked by the simple elegance of how DNA codes and replicates itself. But eventually by the mystery and beauty of a developing embryo, starting from a single cell that divides and divides resulting in the reliable self-assembly of an animal with all its parts! Most fascinating of these, a brain, which in the case of humans, could ask itself, where did I come from? In the end, understanding how interactions between cells in the early embryo determine the early self-assembly of the zebrafish nervous system is what I got to study as a scientist.
Of course, my entry into the KIF1A universe is recent. And the why is simple: beautiful joyous smiling Rohan [Dr. Chitnis’ nephew!]. After having pursued fundamental questions of developmental biology for 25 years, Rohan and his family opened a new door for me. It has been a transformative experience, brainstorming with the KIF1A community and thinking about what we can do that might one day help Rohan and the many children like him with KAND. Thank you, Rohan. I love you.
What do you love most about your job?
Learning. Talking with the people in my lab, discussing their experiments, telling the stories of what their experiments have taught us. Taking disparate pieces of a puzzle and figuring out how they fit together. Especially when we discover how the elements come together to produce an emergent behavior or pattern of development that we would not have ordinarily anticipated. Discovering that “the whole is more than the sum of its parts”. Looking for and learning about deeper organizing principles in biology.
What is the most challenging aspect of your job?
Remembering how easy it is to be wrong when you don’t have enough information. Remembering that an outcome that is consistent with a hypothesis is just that and no more. Sometimes you get a result that you expected from the predictions of your hypothesis but down the road you realize that outcome was for a reason that had nothing to do with your original hypothesis! Don’t fall in love with your favorite hypothesis.
What development are you most excited about in terms of KIF1A research?
De novo KIF1A motor domain mutations associated with KAND have dominant inhibitory effects on KIF1A function. When mutant KIF1A forms a dimer with a wild-type or another mutant copy of KIF1A, it is expected to result in ineffective anterograde transport of bound cargo as the aberrant dimer stalls or moves ineffectively along the microtubule. How to reduce or eliminate these ineffective dimers and how to instead promote formation of wild-type KIF1A dimers, is a central question in trying to help the kids with KAND. In the context of this problem, I was excited to learn that KIF1A is ubiquitylated and degraded in proteosomes, typically following the successful delivery and release of bound cargo at the synapse. One possibility is that if we learn enough about this subject, we might be able to exploit some specific vulnerability of sluggish KIF1A dimers formed with mutant KIF1A and target them for degradation, while allowing functional dimers to continue their journey. Of course, with our current knowledge, it is not at all clear that this will define a viable path to reducing the problem, nevertheless it is what I am excited to learn more about. As a newcomer to research on KIF1A and to translational research, it has been both a humbling and exhilarating experience learning from the extraordinary team of scientists in the KIF1A Research Network. There is much to learn and that has been fun.
I couldn’t get through a day at work without:
Google, a double edged sword! Writing a paper- a thought occurs to me mid-sentence- a new idea! Could it be true? Let’s check on Google! 40 clicks and 40 minutes later, I snap out of the trance and ask, now where was I in that sentence! The internet! Can’t live with it, can’t live without it! Ok, here is a superpower I would not mind. You know all those papers I discover on one of these surfing expeditions, wouldn’t it be amazing if their contents magically got incorporated into my brain, every time I downloaded a pdf to my computer?
I am most motivated by:
Exploring the possibility of a new idea.
When you are not studying KIF1A, what do you do?
I enjoy cooking. During COVID, it allowed me to “travel” the world without leaving the home! I make mosaics, mobiles and kinetic sculptures- an extension of my fascination with “the whole being more than the sum of the parts”. And I am learning to play the guitar-still aspiring for the stage my family members move to the room where I am playing, rather than quietly moving out!
How has COVID impacted your daily work routine?
I have worked from home since March 2020. My unoccupied small office room at NIH has been temporarily converted into a microscope room where lab members can work with safe distancing. I have learnt to manage and interact with lab members entirely with virtual meetings. This was initially weird but has become completely normalized! It has surprisingly added a kind of welcome structure and regularity to some of these meetings. With limited lab members being allowed in each day, the lab members have responded with remarkable teamwork, helping each other to maintain the continuity of their projects. I have been able to read much more working from home, and this has been very stimulating. Working from home has been flexible and fun. Even some time at the end of the day, once a week for a virtual guitar lesson!