HIV-1 control of the human epigenome

Viruses have evolved to navigate cells and take over the cellular processes they need for their own replication. On the other hand the cell will rapidly respond and switch on anti-viral proteins once viral entry is detected. So in addition to taking over the replicative machinery of the cell, viruses need to counter anti-viral attacks to thrive. This project seeks to understand this interaction for Human Immunodeficiency Virus type 1 (HIV-1) infection at the level of transcriptional regulation and epigenomics.

We have made an observation that may give unique insight into how HIV takes over the control of the cell it infects. We observed that HIV specifically induces the degradation of a human cellular protein called RNA polymerase II–associated factor 1 (PAF1) after infection. PAF1 is sometimes referred to as the ‘master regulator’ of gene switching. It controls the production of families of proteins in response to specific environmental responses. For this project you will map the location of PAF1 on chromatin before, during and after infection with HIV-1 and will identify putative gene targets using ChIP-seq analysis. You will link PAF1 location to PAF1-dependent transcriptomic changes upon HIV-1 infection. The dynamics of viral infection on gene transcription can be monitored using a nuclear ‘run on’ analysis, i.e., GRO-seq, to measure the levels of nascent transcription. Genes identified as potentially anti-HIV will be validated using viral replication assays (RT-qPCR, Alu-PCR). You will determine if the signatures are pro-inflammatory which may alert the same or neighbouring cells of an impending infection. Gene and pathways can also be compared with those genes required for HIV replication also observed in genome functional screens.

We are seeking a graduate with interest in combining basic molecular virology with bioinformatics approaches to understanding virus-host interactions. The candidate should have an upper class degree or equivalent in a biology related discipline. Experience in molecular cell biology or bioinformatics analysis would be an advantage but is not necessary. This project will be supervised by Prof Áine McKnight (Centre for Immunobiology) and Dr Miguel Branco (Centre for Genomics and Child Health) at the Blizard Institute. The research project will use molecular biology, cellular biology, next generation sequencing, genetics, and epigenetics. The post is based in the Blizard Institute, Whitechapel Campus. The Blizard Institute provides a stimulating scientific environment and state of the art infrastructure and facilities.