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Tuberculosis is a chronic infectious disease caused by
M. tuberculosis. M. tuberculosis
contains ESX protein secretion system
for the transport of intracellular proteins across their highly impermeable cell wall. Out of five ESX pathways, ESX-1 and
ESX-3 are essential for virulence and growth of
ESX-1 pathway contains at least 10 genes that encode T-cell
antigens as well as AAA-ATPases. Proper functioning of the ESX-1 pathway requires the knowledge of structure and interaction
of multiple ESX-1 substrates and other component proteins prior to their secretion.
We are involved in purification and X-ray crystallographic studies on key proteins involved
pathway. We have purified, crystallized and working for X-ray structures of two key proteins, EspR and EspC. EspR is a
transcriptional activator that promotes ESX-1 secretion by activating transcription of the espACD operon immediately upon
macrophage infection. When the ESX-1 is active, EspR is secreted and result in reduced expression of espACD. Conversely when
the ESX-1 pathway is inactive, the cytosolic level of EspR increases, that results in increased expression of espACD.
EspC is small protein that strongly recognized by T cells isolated from patients with
EspC is immunodominant
in active and latent
infection. The protein contains broadly recognized CD4+ and CD8+ epitopes and induces a
predominantly CD4+ T-cell response. The high immunodominance characteristics of EspC, makes it an attractive vaccine
. The EspC has the high specificity and confers strong potential for T-cell?based immunodiagnosis.
The structure-function analysis of EspR and EspC proteins will contribute significantly in understanding the ESX-1 pathway
mechanism and drug development against
Ajay K. Saxena has completed his Ph.D. degree from AIIMS, Delhi in 1995. He completed his Postdoctoral studies from Austrian Academy of
Sciences, Europe in 1996-98 and NIAID, National Institutes of Health, USA in 1998-2005. Since 2005, he has been working as Associate Professor
at Structural Biology Section of School of Life Sciences, Jawaharlal Nehru University at Delhi, a premier university of India. He has published several
papers in reputed national and international journals and reviewer of several national and international journals. He has obtained several national
and international funding and awards for his excellent research performance.
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