TB Molecular Biology and Signaling Lab @ SVC
Announcement
Internship opportunities for 3 or 6 months available for MSc/MTech students in the area of TB Molecular Biology and Signalling Networks. No fellowships. Interested students may apply by 31st December, 2023 to vandana.malhotra@svc.ac.in
“Research is to see what everybody else has seen and to think what nobody else has thought" - Albert Szent-Gyorgyi
Scope of Work
Worldwide, TB is the second leading cause of death from a single infectious agent. In 1993, World Health Organization (WHO) declared TB a global emergency and warned that the disease could kill 30 million people over the next decade if effective control efforts were not implemented. While significant epidemiological, treatment, and control strategies have been employed over the past decade, the WHO estimate of nearly 30 million deaths was relatively accurate. Globally, one-third of the world’s population is infected with TB, with over nine million incident cases of active TB disease and an estimated 1.3 million deaths occurring per year. With only a partially effective vaccine available and annual increases in the percentage of multiple-(MDR) and extensively-(XDR) drug resistant strains causing disease, the potential for global catastrophe is immense.
Key Areas and Problems
While significant advancements have been made in the field of TB research, we are still far from the development of an efficient vaccine against tuberculosis. A generation time of 18-24 hrs, an impermeable cell wall structure and the unique ability to adapt to the dynamic flux of microenvironments that Mycobacterium tuberculosis, the causative agent of tuberculosis is exposed to during its life cycle inside the human host, are clearly the key factors that have impeded the development of novel anti-tubercular therapies. Through mechanisms not fully understood, M. tuberculosis is able to transition into a state of dormancy or persistence that forms the very basis of the global risk of latent TB today. Latently-infected individuals have a 5–10% risk of developing reactivation TB disease during their lifetime, often due to immunosuppressive circumstances, with HIV infection being the greatest identified cause. Given the critical nature of these adaptive strategies, our knowledge on the regulatory pathways that turn on/off as the bacterium crusades through various stages of infection: survival, growth, persistence and reactivation is very superficial.
Research Interest
Like most bacteria, M. tuberculosis depends on signal transduction systems for transcriptional reprogramming and survival in response to changing in vivo environments. Annotation of the M. tuberculosis genome revealed the presence of more than 200 genes involved in cellular communication and information processing with two component systems (TCSs) and “eukaryotic-like” serine/threonine protein kinases (STPKs) as two major contributors. Understanding how M. tuberculosis signal transduction systems interact and cross-interact to coordinate complex growth, metabolic adaptation, and physiological responses is critical to elucidating the events that govern establishment and progression of tuberculosis disease.
Three general concepts are useful for describing signaling mechanisms: signaling pathways, signaling modules, and signaling nodes. For pathways, the main flow of information is sequential, triggering linear activation of regulatory proteins. Signaling modules are physically linked complexes of signaling proteins and/or scaffolding proteins that make a modular structure within a network, while nodes are capable of responding to multiple signaling inputs, and thus, have many downstream targets. Given our current knowledge and data obtained from my studies, my hypothesis is that M. tuberculosis processes and responds to cellular inputs by controlling signaling events that proceed through linear pathways, modular networks, and multi-dimensional node-based transduction communication.
My lab works on deciphering the underlying mechanisms that drive these networks leading to mycobacterial persistence and dormancy. We use high throughput transcriptomic and proteomic approaches to dissect the signaling networks that govern these adaptations with the ultimate goal of identifying novel drug targets for the design of newer therapeutic interventions.
TB research @ SVC is aimed at leveraging the progress made in the science of genomics, proteomics and cellular imaging to elucidate the key mechanisms of signal transduction in M. tuberculosis and downstream impact on regulation of gene expression and host-pathogen interactions that will promote design of novel disease intervention strategies.
Our Collaborators
About the banner picture : High Resolution Scanning Electron Microscopic Image of Mycobacterium smegmatis