Presenters
William Shih, Harvard University
William is overseeing an effort to apply Synthetic Biology approaches to the development of self-assembling DNA nanostructures and devices for use in biomedical applications. In addition to carrying genetic information, DNA is increasingly being explored for its use as a building material. This new process is called DNA origami because a long strand of DNA can be programmed to fold in on itself to create specific shapes, much as a single sheet of paper is folded to create a variety of designs in the traditional Japanese art...
Ayush Noori, 50 Years Capital
Hi! I am an undergraduate at Harvard studying Computational Neuroscience and student researcher designing machine learning and bioinformatics pipelines to decipher neurodegeneration. I currently work in the Wyss Institute for Biologically Inspired Engineering (advised by George Church), the Department of Biomedical Informatics at Harvard Medical School (advised by Marinka Zitnik), and the Institute for Neurodegenerative Disease at Massachusetts General Hospital...
Serena Zhang, 50 Years Capital
My most valuable skill is responding to emails very fast. Reach me at [email protected]
Ricardo Ruiz, Lawrence Berkeley National Laboratory
Ricardo Ruiz joined the Molecular Foundry as a staff scientist in November 2019. From 2016 to 2019 he was a research technologist at Western Digital working on alternative nanofabrication techniques for non-volatile memories. From 2013 to 2016 he managed a Nanopatterning and Self Assembly group at HGST dedicated to block copolymer and colloidal lithography for magnetic recording. From 2006 to 2013, he was a research staff member at Hitachi Global Storage Technologies where he helped introducing block copolymer...
Nikhil Lyles, Wayfinder Biosciences
Junior at Stanford University interested in CS, Math, and Biomedical Computation
Summary:
What are you trying to do?
We propose self-driving gliders for programmable routing of microscopic cargo on surfaces patterned with dynein motors. We’ll initially focus on two applications: (1) sorting of CAR-T cells to enrich for metabolic fitness and avidity to peptide-MHC targets; (2) DNA-sequence encoded assembly of informational polymers (“makeshift synthetic ribosome”) and subsequent multi-objective evaluation and annotation of functional performance (“Molecular Ninja Warrior”).
How is it done today?
Current cell sorting methods are limited by the assay of choice. The dominant sorting paradigm is FACS; limitations of FACS include the high cost, medium throughput, and limited capability to assay only for staining efficiency.
What is new in your approach?
“Molecular Ninja Warrior”: Gliders enable annotation of library members with transit time through each reaction chamber, which could be a proxy for a rich range of functionally interesting behaviors
If you are successful, what difference will it make?
The ability to assess the anti-tumor activity of specific CAR-T variants would facilitate the development of more effective CAR-T immunotherapies to improve patient outcomes. “Molecular Ninja Warrior”: Small molecule compounds can be assembled with specific activity profiles based on time-tracked performance in sequential reaction chambers. Compounds with desired activity profiles can be identified via high-throughput sequencing for personalized medicine. For example, chemotherapeutics with activity profiles that match the mutational profile of a patient tumor can be selected to prevent drug resistance.
Cost and timeline?
CAR-T cell sorter ($500k per year total cost): Years 1–2 proof-of-principle to demonstrate genotype-specific, DNA-tape-annotated transit times of gliders; Years 3–4 prototyping performance with CAR-T cells; Molecular Ninja Warrior ($500k per year total cost): Years 1–2 proof-of-principle to demonstrate control of genotype-specific routing of gliders for split and combine synthesis; Years 3–4 prototype device for demonstrating library synthesis and functional evaluation.
