Grant: Fellowship - Priority Announcement - HIV/AIDS and/or STBBI

In human cells, DNA is organized in a series of folded structures, such that two distant points on the linear DNA may be brought close together in 3D space through folding. This folded structure allows for interactions between some regions of DNA, while also separating other regions. The folding of the genome dictates the spatial organization of genes and regulatory elements, limiting the possible interactions between them to a few defined combinations and thereby achieving tight control over gene activity. When this organization is disrupted, e.g. by mutation, the normal wiring between genes and regulatory elements can become crossed, and lead to aberrant interactions that activate pro-cancer genes. Viral infections cause 10-15% of cancers worldwide, of which nearly 50% are driven by human papillomaviruses (HPVs). Cervical cancer is the main disease caused by HPV, and in over 80% of cases, viral DNA becomes inserted ("integrated") into the genome of the infected host cell. How viral integration affects the structure and function of the host genome is not fully understood. This study aims to investigate the impact of HPV integration on genome organization and regulation in cervical cancer. We propose to profile DNA folding in patient samples from the HTCMP cervical cancer cohort using a method called Pore-C. This cohort has already been studied in-depth at the DNA and RNA levels, and the additional 3D folding data will allow us to link HPV integration events to specific DNA/RNA dysregulation patterns based on spatial information. This study will help us understand how HPV integration can affect the 3D organization of the host genome and how this contributes to cervical cancer. The insights gained using HPV and cervical cancer as a model system may help inform studies on other HPV-driven cancers, and improve our understanding of how viral integration can impact cancer development in general.