Project details

Despite 10 million cases of tuberculosis (TB) everyone year, we currently have no diagnostic test of current infection. We also can’t predict who, of the estimated quarter of the global population who has been exposed to Mycobacterium tuberculosis (Mtb), will develop TB disease at some stage in their life. 

Using samples collected from a longitudinal cohort of TB household contacts, who are followed for 2-3 years to identify those who develop TB, we are developing a blood signature of TB risk.

This project will use nanopore long-read sequencing to investigate DNA epigenetic markers of TB infection and disease risk and use CRISPR/Cas9 targeting to develop and a multiplex DNA biomarker assay. In vitro Mtb infection assays will be used to understand the impact of identified epigenetic markers on the human innate cell response to Mtb infection.

About our research group

We research how the response of innate immune cells which engulf the tuberculosis (TB) bacteria, namely macrophages, neutrophils and dendritic cells is dysregulated by known TB risk factors. We combine analysis of clinical samples to identify novel pathways of pathogenesis in humans, with in vitro models of TB and HIV infection to identify the molecular mechanism underlying disease risk. 

This includes genetic and epigenetic changes in both the host and bacteria and how these impact the inflammatory response during infection. We conduct biomarker discovery for prediction of infection and TB risk. We are also particularly interested in regulation of cell death and the heterogeneity of cellular responses due to tissue micro-environmental changes which we probe using single cell techniques and advanced live cell imaging.