Leicester Tuberculosis Research Group (LTBRG)

The Leicester Tuberculosis Research Group (LTBRG) is a group of scientists and academic clinicians that is focused on the discovery, development and implementation of knowledge to overcome the health, economic and social impact of tuberculosis (TB) at a local, national and global level.

Our research involves the study of bacterial physiology, host immune responses and clinical disease expression and defining the complex relationships that exist between these domains. The impact of this work includes discovery of novel drug and diagnostic/prognostic targets, determination of immune responses that can inform effective vaccine development as well as biomarkers that offer better characterisation of the host-pathogen relationship, with implementation of this knowledge in experimental medicine studies of transmission and clinical studies of treatment effectiveness.

We have unique access to clinical cohorts with active TB and latent infection (LTBI). Epidemiological studies previously undertaken in these groups has informed National policy change, including the launch in 2015 of a National TB Strategy for England. We have the proven capacity to link bacterial genotyping and physiology to outbreak management. We are developing models of transmission that are entirely novel and involve a multidisciplinary group of engineers, aero-biologists, bacterial physiologists, biological chemists and immunologists. We are pursuing local and international studies of human immunological responses which are integrated into The Gates Foundations interest in vaccine and therapeutics development.

We have overseas connections and collaborations in South Africa, Brazil, The Gambia, China, Kyrgyzstan, and India some of which are established and on-going while others are at the Foundation stage.

Contact: Andrea Cooper or Pranabashis Haldar

Research

Academics in the LTBRG are aiming to identify new drug targets by focusing on the physiology and transmission of mycobacterium.

  • How does M. tuberculosis respond to their environment?
  • How does M. tuberculosis utilise nutrients effectively?
  • How do modifications of M. tuberculosis physiology contribute to success?

Our key areas of research

  • Clinical disease expression
  • Characterising bacterial physiology phenotypes
  • Defining immunological markers of disease
  • Defining complex relationships that exist between these domains

Impact aims

  • Discovery of novel drug and diagnostic/prognostic targets
  • Determination of immune responses that inform vaccine development
  • Determination of biomarkers to characterise host-pathogen relationship

Case study: TB immune responses

An infection model was developed that consists of a low dose mycobacterial challenge, through droplet particles, to the alveolar tissue in the lung. This model allows for very early immune-mediated events in the lung tissue to be dissected regarding kinetics, location and the contribution of specific cell types to immunity. There has been a focus on the role of IL-12, IL-23 and IL-17 and the specific role of dendritic cells and lung resident innate lymphocytes in initiation and coordination of the acquired T cell response. This work was carried out by Professor Andrea Cooper.