Pam Small

Keywords:

Host-pathogen interactions, cellular microbiology, comparative microbial genomics, mycobacterial polyketides

Research Area:

Description of Research:

Among mycobacterial pathogens such as M. tuberculosis, M. leprae and M. ulcerans, it is becoming increasingly clear that lipids play a major role in virulence. In our laboratory we have identified a polyketide-derived macrolide, mycolactone, from M. ulcerans. Mycolactone causes cell death via apoptosis as well as immunosuppression. Information from the genome of M. tuberculosis suggests that similar molecules are also made by M. tuberculosis although the gene products have yet to be identified.

Research in our laboratory is focussed on the identification of polyketide virulence determinants in pathogenic mycobacteria and on understanding how these molecules contribute to the virulence. We are particularly interested in discovering the cellular mechanisms underlying mycolactone-mediated virulence. DNA microarrays of human genes are being used to identify the cellular pathways involved in mycolactone-mediated immunosuppression. Bacterial proteomics is also being investigated as a tool for studying the expression of mycolactone genes in M. ulcerans.

Evidence from the M. tuberculosis genome suggests that in M. tuberculosis polyketide synthase genes are highly mutable. We are interested in the underlying molecular epidemiology of polyketide genes in M. tuberculosis and other pathogenic mycobacteria particularly with respect to the role these molecules may play in virulence.

Contact Information

Pam Small
Molecular Genetics and Systems Biology
Professor, Department of Microbiology

UT
F323 Walters Life Sciences
1414 W. Cumberland Ave
Knoxville, TN 37996
865-974-4042

Email: psmall@utk.edu

Degrees

PhD: Stanford University (1986)