Investigation of the mycobacterial ESX-4 secretion cluster using different biochemical and biophysical methods

Supervision: Christian Magaña Vergara and Dr. Young-Hwa Song

Areas: Molecular Biology, Biochemistry, Biophysics

Description: Mycobacterium tuberculosis (Mtb) is one of the most clinical important pathogens in the world. Extensive research led to the discovery of a specialized secretion system in Mtb dedicated to export a set of immunomodulatory effector proteins. This system is designated as the new ESX secretion system, eponym from one of the first identified substrates ESAT-6. The genome of Mtb devotes one percent of its coding capacity to five ESX clusters, designated ESX-1 to ESX-5. The clusters ESX-1, ESX-3, and ESX-5 have been analysed in detail. However, the function of both ESX-2 and ESX-4 remains unknown.

The aim of this project is to determine the structure and molecular function of the ESX-4 cluster. To achieve this goal, the ESX-4 of Mtb has to be expressed and purified from Mycobacterium smegmatis. Once purified, the ESX-4 complex will be characterized using several biophysical methods such as cryoelectron microscopy and single molecule spectroscopy.