Transcriptomic analysis of CNS TB

Project title
Transcriptomic analysis of CNS TB

People involved
Principal investigator : Prof Muazzam Jacobs
Co-investigator: Nai-Jen Hsu
Collaborator: Natalie Nieuwenhuizen (Max Planck Institute for Infection Biology)
Bioinformatics support team: Katie Lennard

Short description of project
Tuberculosis of the central nervous system (CNS-TB) is the most severe form of tuberculosis which often associates with high mortality. Moreover, Mycobacterium tuberculosis (M. tuberculosis) infection in the CNS causes the most devastating manifestation leading to severe neurological complications and morbidity. An attenuated vaccine, Bacillus Calmette-Guerin (BCG) is widely used to prevent TB, which have demonstrated various protections against CNS-TB and other neurodegenerative diseases. Little has understood of the cells that regulate infection, the respective functions and contributions of different cell types to overall protection of the CNS. There is an urgent need for understanding basic cellular and immune functionality.

The CNS is an immune-privileged site which is highly regulated to control access to the CNS tissue. This is designed to maintain homeostasis and limit potential pathology damage. In response to M. tuberculosis infection, CNS resident cells produce pro-inflammatory cytokines that leads to neuroinflammation and subsequent structural destruction or neurophysiological dysfunction. Although microglia are the principle targets of M. tuberculosis infection in the brain, other CNS cell types such as astrocyte and neurons can internalize M. tuberculosis bacilli, and thereby elicit an immune response. This project aims to investigate the immune response of astrocytes, neurons and microglia during exposure to both virulent (H37Rv) and non-virulent (BCG) mycobacterial strains. Clarifying the nature of the immune responses of the resident CNS cells will be beneficial to improved vaccine development and therapeutic strategies.

Objectives
Perform differential gene expression analysis of microarray-based gene expression data, comparing CNS cells (astrocyte, neuron, microglia) infected with H37Rv or BCG.