Gene expression, regulation and pseudogenes in M. leprae
Investigator: Diana Williams, Ph.D .
The genome of M. leprae is highly degraded and possesses the largest repertoire of pseudogenes compared to other bacteria as well as a large number of deleted genes. This large-scale loss of gene function has resulted in a genome that is occupied by less than 50 percent protein-coding genes and comparative genome analysis has identified deficits in several general cellular metabolic families.
The National Hansen's Disease Program has used the M. leprae genome sequence data, bioinformatics and surrogate genetics in several mycobacterial hosts to study specific M. leprae genes associated with drug resistance, gene regulation, virulence, and growth. In addition, we have assembled the first comprehensive transcriptome of M. leprae and are exploring its functional metabolic pathways.
Dr. Williams' work continues to be at the forefront of understanding M. leprae genetics and has resulted in molecular tests useful for diagnosing Hansen's disease and determining M. leprae's susceptibility to antileprosy drugs.
Genotyping M. leprae using variable number tandem repeats
Investigators: Richard Truman, Ph.D.
Understanding the mode(s) of transmission of leprosy is a major goal of leprosy research. Defining this epidemiologic parameter should help clarify risk of infection and may help direct public health intervention strategies aimed at controlling leprosy.
Mycobacterium leprae is an obligate intracellular pathogen that is widely distributed around the globe. There are no recognized sub-types and the bacillus exhibits little genetic diversity as judged by common DNA sequence structures. Work is underway to establish a panel of reliable molecular markers to be used to track M. leprae transmission in the community Initial studies have been focused on establishing the link of zoonotic transmission between armadillos and humans in the southern United States, And additional field studies are underway in India, Brazil, and the Philippines.
Mycobacterium leprae cultivation
Investigators: Ramanuj Lahiri, Ph.D. & Diana L. Williams, Ph.D.
Mycobacterium leprae is yet to be cultured in artificial medium, making it one of the most intractable microorganisms to study. Completion of the M. leprae genome sequencing indicates the deletion or partial deletion of multiple genes, notably those involved in respiratory chains, iron acquisition, and other metabolic processes. Since these deletions would not necessarily preclude culture medium supplementation with defined metabolites, we are designing different growth media formulations taking cues from the M. leprae genome, transcriptome and other biochemical studies.