Snow Lake - Snoqualmie Pass - Fall 2018
Benjamin Basanta

I am a Research Associate in the Lander Lab, at The Scripps Research Institute, working on transthyretin amyloidosis. We use cryo electron microscopy to find how transthyretin (a protein that carries the hormone thyroxine and retinol in human blood) looses its normal structure and forms the amyloids that are characteristic of transthyretin amyloidosis. We hope that better understanding the molecular mechanisms that lead to amyloid formation will lead to better therapies, prevention, and possibly shed light on how other types of amyloidosis develop.

During my Ph.D. in the Baker lab , I focused on designing proteins from scratch to help us understand how proteins fold, and advancing our ability to make proteins with completely new functions. We described a set of principles for designing an intricate structural motif, curved sheets, found in proteins with diverse functions. In order to do this, we analyzed curved sheets in known protein structures and proposed a number of priciples, which we then tested by making proteins from scratch. Up-to-date code for generating proteins with curved sheets can be found in this GitHub repo. I then used the above principles in a generative algorithm that explores a wide range of protein structures with the goal of creating custom-tailored scaffolds for novel functions. In order to widely explore structural space while generating physically realistic solutions, we refined the algorithm using cycles of design and testing. To measure the stability of our proteins in real life, we made them inside cells and obtained experimental data for large numbers of them. We applied machine learning on these data to find out what features predict well-folded designs. Feeding that information back into the generative algorithm increased its success rate. This research was the subject of my 2019 Protein Society Annual Symposium poster, and a manuscript in preparation. Parallel code for optimizing the multiplex gene assembly method used in this work, based on the original publication, can be found in this GitHub repo.

I majored in Biology in 2012 from the Universidad de Buenos Aires (Argentina). During my undergrad I spent eight months at Janelia Research Campus, supervised by Loren Looger, where I worked on new bimolecular tools to follow dopamine-related activity in live brains. I presented this work as my Licenciatura thesis. Shortly after graduation I became an advisor in the 2013 Buenos Aires iGEM team, which won the gold medal for best mathematical modeling. In the time between graduation and leaving for grad school, I worked for a year and half in the Nadra laboratory, at FCEyN-UBA, designing zinc-finger proteins to recognize specific DNA sequences. I presented this work in a poster at the "3er Congreso Argentino de Bioinformatica y Biologia Computacional" Conference in 2012.

Benjamin Basanta
Lander lab - 10550 North Torrey Pines Rd. TRY-21
La Jolla, CA 92037