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New Engineering Tools for Investigating Cellular Reprogramming

Seed Grants
Awarded in 2014

Interdisciplinary Initiatives Program Round 7 - 2014

Joseph Wu, Medicine, Radiology
Nicholas Melosh, Materials Science & Engineering

Over the past 7 years, the advent of human induced pluripotent stem (iPS) cells has generated significant interests among biologists and clinicians. However, progress is currently mired by the available biochemical transformation and analysis techniques, which are inefficient, cumbersome, slow, and expensive. Importantly, how a somatic cell becomes reprogrammed into iPS cell is not entirely known. To make iPS cell a clinical reality (e.g., generation of cell banks for drug screening and personalized medicine), a new set of specific tools is necessary. We believe many of the procedures that are hampering progress are highly amenable to engineered solutions, yet the need for them has not been recognized by either the engineering or biology community. This proposal will merge the expertise of a stem cell biologist in the School of Medicine and an electrical engineer in the School of Engineering to develop a novel “nanostraw” platform that will passively sample intracellular protein contents over a period of 21 days during the reprogramming process. This platform directly pierces the cell membrane with ~100 nm diameter ‘nanostraws’, allowing cytosolic molecules to slowly diffuse out of the cell, but without rapid enough loss to cause cell death. We will use this platform to extract cytosolic proteins and deliver them to the already developed nanoscale detection schemes. Our goal is to understand how intracellular protein changes occur during the reprogramming process, which will shed significant biological mechanisms and lead to better clinical applications to impact the healthcare delivery in the future.