Project 466513

The field of molecular genetics is budding, and advances in recent years have enabled the investigation of health at a genetic level. However, there is a large gap in the knowledge regarding the effects of single-nucleotide mutations and how these may predispose us to disease. One of the most pervasive and enigmatic health concerns is the development of genetically predisposed cancers. Currently most mutations in the genome are classified as variants of unknown significance, such that a variant cannot be classified as benign or pathogenic; this dramatically hinders a clinically meaningful interpretation of variants. My research project aims to develop a novel high-throughput cellular assay to determine cancer risk based on variants of single-nucleotide mutations. The subsequent generation of variant effect maps will function to assess cancer risk in the human population. This will be made possible using a technique known as deep-mutational scanning to reveal the properties of variant proteins, coupled with a novel multiplexed phenotyping strategy that I have developed. This research will profoundly affect the understanding of oncogenic variants and will contribute to a larger atlas of variants to determine cancer risk. The construction of this methodology is imperative as all functional genetic variants compatible with life exist in approximately 1 in 50 people living today. The ability to provide personalized care will fundamentally rely on this type of genetic investigation. As variants continue to be mapped, this methodology will radically alter the way we perceive and apply personalized health care through precision medicine not only in terms of cancers, but genetically related disorders at large.