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Mamta Rawat, Biology.

My research concerns the role of two distinctive thiols, ergothioneine and mycothiol, in pathogenesis and bioremediation. Mycothiol is found exclusively in actinomycetes like Mycobacteriium tuberculosis, the causative agent of tuberculosis, and the genus Rhodococcus which contains species involved in bioremediation. All four genes coding for enzymes involved in the biosynthesis of mycothiol have been identified and characterized. Mutants in genes involved in mycothiol biosynthesis are more sensitive to oxidative stress and stress caused by toxins such as antibiotics and alkylating agents indicating that mycothiol serves as a coenzyme or cofactor in detoxification reactions. My laboratory is interested in identifying these mycothiol dependent proteins using conventional protein purification, random and targeted mutagenesis, and reverse genetics. We are particularly interested in the identification and characterization of mycothiol dependent peroxidases as these enzymes may play a major role in the pathogenesis of tuberculosis by aiding in the survival of M. tuberculosis in macrophages and the “granulomas” of the lungs.

In contrast to mycothiol, ergothioneine is detected in most organisms including humans where it is believed to be derived from the daily diet. Although ergothioneine is found everywhere, little is known about its purpose and it has been demonstrated that only fungi such as Neurospora crass and mycobacterial species synthesize this thiol. We are screening transposon mutant libraries for mycobacterial mutants lacking ergothioneine with the overall aim of identifying genes involved in the biosynthesis of ergothioneine. Characterization of mutants lacking ergothioneine will give us an indication about the role of this thiol in mycobacteria and eventually humans.

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