Understanding the mechanism of NK cell inhibitory receptor Ly49A variegated expression

Summer 2018

Susanna Ming-Yu Dang : MCB: Genetics, Genomics & Development

Mentor: David Raulet

Lymphocytes are a type of white blood cell that are essential to the function of vertebrate immune systems. Lymphocytes include Natural killer (NK) cells, an important component of the innate immune system. NK cells function through families of stimulatory and inhibitory receptors, providing early response to viral infections and tumor development. In mice, Ly49 C-type lectin receptors make up the largest family of inhibitory receptors expressed on NK cells. NK cells require Ly49 receptor activity in order to discriminate between healthy host cells and infected or abnormal cells and respond accordingly. NK cells express on average one to four of ten Ly49 genes in an independent, variegated fashion (only subsets of NK cells express each given Ly49 gene). My project aims to learn more about what regulates NK cell variegated expression of Ly49a as a model gene for the cluster. Based on previous studies, I hypothesize that DNA elements acting alone or in concert control Ly49a variegated expression. I will be deleting DNA elements in hematopoietic progenitor cells (HPCs) and adult NK cells using the CRISPR/Cas9 system to test for changes in NK cell Ly49a expression. Understanding the mechanism of Ly49a variegated expression will inform us on a fundamental outstanding question in NK cell biology. In addition, this will give insight into many other development systems that involve stochastic gene activation events.

I would like to thank the Rose Hills Foundation for their generous support of my project this summer. This project was an incredible learning experience that allowed me to greatly expand my skills and knowledge. The opportunity to work independently was one of the best aspects of this experience. I am excited to finish my senior thesis and eventually go on to graduate school.