Brian Shami-Inkindi

What is your research project on and why is it important?

My project centres on Aurora-A, a serine/threonine kinase vital for cell cycle regulation, particularly in mitotic entry and spindle assembly. Given that its dysregulation contributes to the development of various cancer types, Aurora-A is a promising target for cancer therapy. Traditional kinase-targeting therapeutics face challenges like resistance, off-target effects, and limited efficacy, highlighting the need for alternative approaches. My project aims to isolate Affimers (an antibody-mimetic protein) targeting various Aurora-A binding sites to characterise its specific interactions and their phenotypic effects.

This project is important as these Affimers are expected to offer new insights into Aurora-A's expanding biological roles related to previously unknown/inaccessible epitopes which potentially may lay the groundwork for a new generation of anti-cancer therapeutics.

What facilities and specialist equipment do you use to help you carry out your research?

Aurora A kinase requires use of the AKTA® pure system for efficient protein purification, so I often end up in the PIXC (Protein, Interactions, X-Ray and Characterisation) whenever it’s time for another protein prep. My future work will also involve use of the SPR and ITC equipment within the PIXC facility, to help quantify the binding dynamics of my Affimers with Aurora-A

As my project progresses, I will need to produce protein crystals for x-ray crystallography so will make use of the mosquito® LCP within the Garstang Level 4 labs for setting up crystal trials. This will help me structurally determine where exactly my Affimers bind on Aurora A.

What do you particularly enjoy about your research?

My project direction isn’t rigorously set, but wholly determined on what the effect my Affimers have on Aurora-A. Therefore, this gives me an opportunity to learn a wider range of techniques and skills as well as collaborating with various people across disciplines which should be the case throughout my project. I enjoy this nature of my project, as it keeps me deeply engaged and invested in my research. My lab also has a very friendly working environment, filled with lovely colleagues who are always ready to lend a hand—or have a pint at the local pub!

Why did you choose to undertake a PhD at the University of Leeds?

My motivation for undertaking a PhD stem from my lifelong fascination with complexities of life and my ambition to make meaningful contributions to the world. I graduated from the University of Leeds with a Master of Biology (MBiol) degree in Medical Biochemistry, with my Masters research project helping nurture a strong foundation in academic research with that experience cementing my desire to work in a laboratory setting. The University of Leeds is already one of the best research environments in the country with me already having firsthand experience of working here, it only felt natural to continue.

Who are your supervisors? How have they helped you with your research so far?

I am primarily supervised by Dr. Darren Tomlinson, with co-supervision from Prof. Richard Bayliss and Prof. Colin Johnson. Their support have been instrumental in helping me navigate the challenges of my first year and overcoming the project's occasional "growing pains." Each of their differing areas of expertise has been invaluable in shaping my research, making it well-rounded and comprehensive. Additionally, they have provided me with access to a wide range of scientific networks and collaborations, most notably SPIDR (Structures and Probes of Intrinsically Disordered Regions (spidr-slola.com)).

What are your plans after you complete your PhD?

At this stage in my career, I'm still exploring my options. A post-doc would interest me, depending on the project, but I'm also keen to gain experience in the biotech industry. I think it’s too early for me to decide!