In my project, I am highly interested in intrinsic immunity, specifically, understanding the mechanism of host restriction factors against retroviruses and retrotransposons. My work focusses on the human restriction factor TRIM5α and how this protein serves as guardian of the genome’ by restricting LINE-1 retrotransposition. Previously, our laboratory has shown that TRIM5α senses cytosolic LINE-1 RNP complexes and initiates innate immune signaling via NF-kB and AP-1 to block the LINE-1 promotor. One aim of my project is to elucidate this signaling cascade and pinpoint factors that contribute to downregulating LINE-1 expression. Another major part of my work deals with assessing the protein-protein interaction between TRIM5α and LINE-1. To this end, we employ a multitude of methods to analyze this interplay in vitro and in vivo. This will also provide novel insights into LINE-1 biology by describing the structure of LINE-1 RNPs. Given that the role of LINE-1 elements in the context of tumorigenesis, aging, and autoimmunity is increasingly being recognized, understanding LINE-1 biology and determine possibilities to limit LINE-1 activity is paramount to interfere with disease progression. Being aware that TRIM5α potently restricts LINE-1 retrotransposition, fully uncovering the underlying mechanisms in concert with evaluating the significance of the TRIM5α-mediated inhibition in clinically relevant samples will push the field on how to cope with LINE-1 abnormalities.
