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Molecular Epidemiology

Functional Genomics:
Elucidation of the genes involved in biosynthesis of M. leprae PGL-I is underway. Rama Murthy Sakamuri is presently working on this project using a combination of genetic tools and biochemical assays.
Refining the Proteome:

A combination of approaches are in use: recombinant cloning and expression of M. leprae genes of unknown function; the generation of antibodies to recombinant proteins; the extraction and separation of proteins from clinical and reference materials [armadillo derived infected tissue]; detection and identification using antibodies and clinical sera.

Epidemiology of leprosy: Molecular typing of M. leprae

The mechanisms of transmission of M. leprae, the causative organism of leprosy are still unclear with respect to the source, reservoir, mode of transmission and interaction with the host. Multiple hypotheses exist, but answers remain speculative owing to the inability to cultivate M. leprae in vitro, the slow onset of disease, and the broad spectrum of clinical manifestations. The recent availability of the genome sequence of an isolate of M. leprae is a valuable new resource applicable to the epidemiology of leprosy.

It is important to prove identity of M. leprae within the chain of transmission. The identification of new polymorphic loci based on the principle of variable number of tandem repeats (VNTRs) and the development of robust technologies for strain typing are a key component of our research activities.

We have now established an international research consortium with the aim of a concerted effort to study multiple factors in order to obtain a more comprehensive understanding of the most plausible causes for continued incidence of leprosy in the endemic areas.

Drug Resistance:
We are developing and implementing routine molecular surveillance for drug resistance in leprosy patients (primary and relapsed cases) in various endemic communities. Genomic DNA from biological samples such as slit skin smears and biopsies are subjected to PCR based tests for detection of mutations that confer resistance to Multidrug therapy (MDT) drugs dapsone and rifampicin, and alternative anti-leprosy drugs such as oflaxacin.

Projects such as these require considerable discussion, research and collaboration. Any ideas, suggestions or comments from the research community are welcomed. Please e-mail your comments to vvissa@colostate.edu

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