First person – Aadil Qadir Bhat and Mir Owais Ayaz Free

Aadil Qadir Bhat

How would you explain the main findings of your paper in lay terms?

A.Q.B.: Since IGF1R dysregulation causes cancers, targeting IGF1R is pursued with great interest, particularly for the treatment of breast cancer. However, drugs like kinase inhibitors that target IGF1R inevitably target insulin receptors as well, thereby resulting in many complications including hyperglycemia. In this study, we have identified and characterized an allosteric inhibitor-binding pocket in IGF1R that could be exploited for designing inhibitors to specifically target IGF1R. This will assist in developing IGF1R protein-specific anti-cancer agents for treating these cancers.

M.O.A.: IGF1R is a receptor tyrosine kinase like its homologous protein insulin receptor. IGF1R is dysregulated in cancers. However, targeting this protein with kinase inhibitors inevitably targets insulin receptor as well, thereby altering glucose metabolism. Identification of an allosteric inhibitor-binding pocket in IGF1R will help to overcome this problem and will facilitate development of IGF1R specific allosteric inhibitors that can help in cancer cures without targeting insulin receptor.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

A.Q.B.: The most striking result for me was the identification of three amino acid mutations (E1056G, R1064K and L1065A) outside the ATP-binding domain of IGF1R that lead to the abrogation of kinase activity of IGF1R. Upon mutating these residues, IGF1R was seen to lose its kinase activity. This was the moment that gave us happiness and prompted us to move forward in examining in-depth the role of these residues on various activities of IGF1R.

Why did you choose Journal of Cell Science for your paper?

A.Q.B.: We chose JCS because this journal publishes beautiful and cutting-edge science covering the full breadth of cell biology and molecular biology topics as well as encompassing all aspects of structural biology.

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

M.O.A.: Yes, our supervisor Mohd Jamal Dar has been fully involved not only in supervising this project but helping us to grow as active and independent researchers. He has been pushing us to keep track of the most up-to-date literature and continuously encouraging us to come up with new ideas and suggestions.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

A.Q.B.: The gratification of overcoming an obstacle is my greatest motivator. Science has never been my best subject, but I opted for it because I wanted to prove to myself that I could do it. The course wasn't easy and I spent many nights studying late but I passed with an ‘A’. The feeling of accomplishment that comes with exceeding challenging goals is what drew me to a career in science. I'm motivated by the fact that, at the end of my research career, I know I've helped make a difference in the lives of my patients and their families. Seeing the smiles on their faces and watching them improve will make me look forward to work even more. That's why I became a science student and why I'm pursuing a position in research.

Who are your role models in science? Why?

A.Q.B.: Marie Curie and Albert Einstein. As the first woman to receive a Nobel Prize in 1903, radiology pioneer Marie Curie is often recognised as the world's most famous female scientist. Not only did Curie discover two new chemical elements – radium and polonium – but she saved countless lives on the battlefield during World War I. By bringing her advanced theoretical knowledge to the front line, Curie was able to set up 200 stationary radiological units and equip a fleet of specialist vehicles with X-ray technology. She taught herself how to operate the equipment, drive her new vehicles and fix any mechanical issues – as well as inspiring many other women to do the same.

Einstein was incredibly kind, caring and impassioned. He made some quotes in ways that would make less educated or less intelligent people still feel good about themselves. Einstein was unphased by ‘consensus’. When a paper was written stating, ‘100 German Scientists Against Einstein’, his reply was, “If I was wrong, it would only take one of them”. Einstein had a wry and healthy sense of humour and viewed the world as a positive place, hopeful and full of opportunity. He liked humans/humanity. He did not like war, he did not like weapons or killing. Most importantly, Einstein argued in support of Louis de Broglie's ‘Pilot Wave Theory’ at the 1927 Solvay Physics Conference, putting him ahead of most others attending that conference in terms of his overall intelligence and wisdom.

What's next for you?

A.Q.B.: My research experience provides me with skills to plan, implement, and analyze data from experimental studies. I anticipate that successful publication of my research work will assist me in obtaining an independent position after some years, to start my own research program, and to fulfil my goal of becoming an independent scientist.

M.O.A.: Being an experimental research scientist is a way of life for me. I enjoy working in the laboratories and explore new things. I aim to continue working as a researcher and collaborate with scientists across the globe to further my chosen career.

Tell us something interesting about yourself that wouldn't be on your CV

A.Q.B.: I am an intensely dedicated and self-motivated professional with incredible teamwork capabilities and an overwhelming ability to see every single project from conception to completion. While maintaining a professional environment, I have the ability to connect on a personal level with everyone in the workplace and have a passion to stay updated with current and new technologies.

A.Q.B.: I am constantly in search of things that challenge me and help me grow. I am an amateur swimmer. I started learning swimming out of interest sometime back. I am not a professional swimmer nor have I won any competitions, but this was always something I wanted to do. I am a happy-go-lucky person. I always try to be optimistic and help others to cheer up.

A.Q.B. and M.O.A.: Sometimes research ideas flourish when you are on a long drive. Three years back, we were travelling together with our supervisor and we decided to map this newly identified binding pocket in IGF1R to examine the impact of all the conserved residues on various activities of this protein with the long-term goal to screen compound libraries using this binding pocket for the identification and development of allosteric inhibitors.