General Biology Seminar
Cells operate through molecular circuits – they sense environmental inputs, perform biochemical operations, and generate phenotypic responses. Deciphering their wiring diagrams in both health and disease is a major scientific goal. Advances in nanotechnology now allow us to generate structures with well-controlled shapes, compositions and surface chemistries at sizes comparable to biomolecules and cells. These can be applied to systematically uncover key biomolecular components and their interconnections. Here, I will describe perturbation and observation strategies that I have developed and implemented to investigate cellular circuits, including those of immune cells. I will present two approaches – one that uses nanowire delivery to perturb cellular behaviors and another that uses microfluidic processing to observe them. To perturb, I fabricated arrays of vertical silicon nanowires to administer biomolecules into living cells in a minimally invasive fashion. I will show how we leveraged this platform to help systematically dissect the circuits that control the differentiation of autoimmunity-inducing Th17 T cells. To observe, I developed integrated microfluidics methods for measuring genome-wide mRNA profiles from many individual cells. I will explain how we utilized this approach to study the intra- and inter-cellular circuits that drive the dendritic cell response to pathogens. I will conclude by highlighting future prospects for nanotechnology to aid us in resolving the intra- and extra-cellular factors that drive ensemble behaviors so that we can disentangle interacting cellular systems from the "bottom-up".