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• infectious disease and the immune system

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Immunotherapy

IMMUNITY AND INFECTION: Tuberculosis (TB) is the biggest killer infection. We have no good TB vaccine, TB treatment takes too long, and multiple drug resistant TB is on the march. At St. James? Hospital, our research might lead to new vaccines and immuno-therapies for this global health emergency.
We team up with TCD immunologists to work with the hospital TB service, and the national reference laboratory. Together, we make research breakthroughs that are published in Cell, The American Journal of Respiratory and Critical Care Medicine, Immunity and the Journal of Immunology. We mentor physicians, from any speciality, to a PhD Doctorate. We study the host response to TB, so that we can invent new therapies; for example, we are developing inhaled micro-particles to re-programme human alveolar macrophages in diseased patients.

With our TCD TBSI collaborators, we define the host response to Mycobacterium tuberculosis (Mtb) infection, to uncover new therapeutic targets that support the patient.
If you join us to do your PhD, your thesis work will be supervised by clinical and PhD mentors.

1. Immunometabolism tuberculosis (co-PI Luke O Neill)
We were the first to publish on the immunometabolic changes seen in the human response to Mtb infection. This project will further explore these pathways and exploit therapeutic options now available to manipulate metabolism so we can generate new vaccines and host directed therapy.

2. Lipid metabolism and tuberculosis (co-PI Fred Sheedy)
We have published on how Mtb manipulates the macrophage, so that it can serve as a reservoir cell for the pathogen. After infection, foamy macrophages develop, which protect the bacillus from the immune response. We will find out how lipid metabolic changes generate this reservoir cell for the parasite, and how to prevent its emergence.

3. DNA sensing and type 1 Interferon production as an immune evasion strategy (Co-PI Andrew Bowie)
Mtb DNA can be detected by the invaded macrophage. Special sensing proteins start a signal that leads to type 1 interferon production, which suppresses TB immunity. The TBSI group have discovered new parts of this DNA sensing pathway in tuberculosis and BCG infection. This project will figure out how this leads to a failed TB immune response, and how to fix this.