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Technologies

About the lab

Tuberculosis (TB) remains humanity’s longest pandemic infection, and the leading single cause of global infectious mortality. As humans have co-evolved with Mycobacterium tuberculosis (Mtb), most adults and children develop natural protection – only 5-15% of those infected ever develop disease, generally within 5 years, although it can take decades. With an estimated 2 billion people having been infected globally this results in 10 million people diagnosed with TB and over 1 million deaths, annually. Our inability to eliminate TB is due to its immunological manifestations profoundly challenging our fundamental understanding of what constitutes and mediates protective immunity and disease risk. There is also currently have no diagnostic test that can identify individuals infected with Mtb, and critically, who of those is most at risk of developing TB and thus should be prioritised to receive treatment.

The Coussens Lab studies how the response of innate immune cells, namely macrophages and neutrophils, that engulf the TB causing bacteria is dysregulated by biosocial and co-morbid factors that increase risk of TB development. We combine analysis of clinical cohort samples to identify novel pathways of pathogenesis in humans, with in vitro infection models to determine the molecular mechanism underlying disease risk. Together this enables us to identify novel therapeutic targets and develop diagnostic biomarkers to improve earlier TB diagnosis and inform who will most benefit from treatment.

We achieve this using a range of cutting-edge techniques to interrogate genetic, epigenetic, transcriptomic and proteomic changes in both the host and bacteria to identify how these impact the inflammatory response during infection. To study the regulation of cell death pathways and the heterogeneity of cellular responses due to tissue micro-environmental changes we probe these using single cell omics, spatial omics and advanced live cell imaging techniques.

Our mission

The majority of people who get infected with the TB bacteria do not get sick. Yet, also having HIV-1 or SARS-CoV-2 infection, diabetes, or being malnourished can increase the risk of developing TB and lead to more severe disease. Our research focuses on understanding how these risk factors dysregulate normal immune cell responses during infection, resulting in TB development instead of bacterial clearance. We are particularly interested in the different way these pathogens cause infected cells to die and how these forms of host cell death destroy the architecture of the lung and other sites of infection, allowing the bacteria to spread and cause disease. Given that tuberculosis is transmitted by coughing, following damage to the lung, the only way to eradicate TB is by stopping people developing disease once infected.

Our Mission is to identify the molecular mechanisms by which lifestyle and life-course factors modify immune cell functions increasing an individual’s susceptibility to tuberculosis, to inform development of screening biomarkers of TB risk and more personalised immune-defect targeted therapeutics to restore natural immune protection. Together these tools will enable us to identify and treat those most at risk of developing and transmitting TB. We believe such an approach has far greater ability, than antibiotics alone, to prevent current and future TB, providing the greatest long-term cure from TB and stoping TB transmission.

Impact

  1. Identifying pathogenic mechanisms to inform biomarkers and immunotherapeutics for TB and COVID-19
  2. Characterising the detrimental interactions of HIV-1 and SARS-CoV-2 on TB pathogenesis
  3. Undertaking international cohort studies that challenged the prevailing paradigm that the majority of latent TB that progresses to disease exists in a quiescent state for years prior to TB reactivation
  4. Raising the international research community awareness that asyptomatic TB can exist for years before detection and early treatment is critical to reduce onwards transmission and poor patient outcomes
  5.  Working with the WHO to acheive policy change, with asymptomatic TB now defined as a distinct disease state to detect and treat to prevent symptomatic TB development.
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