Technologies for assaying the spatial position of biomolecules in situ

Abstract

As cells receive and send complex signals over varying distances the spatial position of a cell is fundamental to defining its current and future identity. With the advance of single cell genomics technologies over the past decade we are able to understand cellular signals at an unprecedented scale. However current methods for sampling single cells do so outside of the tissue context in which that cell came from. Thus there is a need to study cellular signals in native tissue context at the resolution of individual cells to understand fundamental biological processes. Ideally one would also study signals in an unbiased, untargeted manner. In this dissertation I outline efforts to develop such technologies. Importantly, the methods disclosed in this document are broadly applicable to any tissue specimen revealing organizational principles across many different tissue environments and biological settings including the study of human specimens.