Hey! I am Satyam Kumar Yadav, I just finished my Integrated Masters in Life Sciences from NISER Bhubaneswar India Over the past few years I got really interested in how proteins work especially how their shape and movements affect what they do, I ended up working on structural and computational biology projects using simulations and modeling to explore these questions. Outside of science I read and write poems, listen to all kinds of music, I also love playing cricket, badminton, walking, occasional running and watching movies.

I am really looking forward to being part of the Cilia AI program learning from people around me, contributing in whatever way I can and growing through the whole process.

Artificially designed protein binders to investigate intraflagellar transport in ciliogenesis

AI-based methods now allow for accurate structure prediction of protein complexes using AlphaFold as well as the design of artificial proteins with specifically tailored functions. These developments will be leveraged to design artificial proteins to bind and alter the function of the intraflagellar transport (IFT) machinery, which is essential for ciliogenesis. It was recently shown using Alphafold modelling and electron tomography that the IFT complex can adopt two widely different conformations relying on different protein interfaces of the same protein subunits. We hypothesize that each of these two conformations is required for IFT to the ciliary tip (anterograde IFT) and back to the ciliary base (retrograde IFT), respectively. To investigate this hypothesis, we will design artificial proteins to bind IFT88 or the IFT52/46 sub-complex that are predicted to block each of the two observed IFT complex conformation. These binder proteins will be validated in silico using AlphaFold and purified to experimentally confirm the predicted function using pull-down assays with purified components. Successful binders will be introduced into Chlamydomonas reinhardtii and mammalian RPE cells and the impact on IFT and ciliogenesis monitored, which will allow us to unravel the function of different IFT complex formations in anterograde and retrograde IFT. Additionally, a local pipeline running AlphaFold 3 will be utilized to uncover novel ciliary cargoes of the IFT system followed by experimental investigation of predicted cargoes.