I head the Host-Directed Therapeutics group and have expertise, leadership and training required to carry out research in the area of host immune response to Mycobacterium tuberculosis to investigate host genes as potential targets for the development of host-directed therapies. I have a broad background in molecular biology, with specific training in membrane traffic and expertise in macrophage response to various mycobacterial strains. I have also extensive experience in transcriptome analyses. Our research into mouse and human macrophage global gene expression was a great stepping stone to investigate the role of the identified genes in the killing of M. tuberculosis. In current projects, my laboratory will carry out RNA isolations, RT-PCR, CFUs etc. from human blood monocyte-derived macrophages (isolated from healthy individuals) infected with pathogenic (clinical multi-drug resistant isolate R179) and treated with nanoparticles containing gene-specific vectors.

In the past, researchers have carried out numerous investigations on macrophages infected with mycobacterial strains that have been cultured in the presence of detergents such as Tween-80. We are one of the first research groups to employ mycobacteria uniquely cultured and filtered in the absence of detergent. We performed a genome-wide RNA-Seq gene expression analysis on mouse bone marrow-derived macrophages infected with mycobacteria cultured in a detergent-free media. We demonstrated that a robust response occurred when we used detergent-free mycobacteria as compared to mycobacteria cultured in the presence of Tween-80. We further showed that the macrophage response to hypo- and hyper-virulent clinical mycobacterial strains differed dramatically and identified host candidate genes potentially related to hypervirulence. We then followed up these high throughput assays and investigated the role of top differentially expressed genes in the killing of mycobacteria in macrophages. We employed siRNA knock down and vector based induced expression of these genes to demonstrate their individual contribution. We demonstrated that OAS1, OAS2, OAS3 and OASL are involved in the killing of mycobacteria in THP-1 macrophages.

We conducted a global transcriptomic analysis of human blood monocyte derived macrophages infected with pathogenic and non-pathogenic mycobacteria. Differentially expressed genes were validated through qPCR and Western blots. Vector-based overexpression of the genes IFIT1, IFIT2 and IFIT3 resulted in increased killing of M.tb identifying them as targets for the development of host-directed therapeutics for the treatment of tuberculosis. An International patent application number PCT/IB2020/059466 in the name of Stellenbosch University entitled “IFIT Polypeptides and Uses for Treating Tuberculosis Infection” has been published on 15 April 2021 by the International Bureau of WIPO with Publication number WO 2021/070107 A1”. Inventors: Bienyameen Baker, Abhilasha Mishra. The National Phase applications In South Africa, USA and Germany was initiated on 13 April 2022