Science for Health
08 March 2012
Two new programme leaders track joined the Institute in 2011 to set up new research programmes.
Institutes like NIMR thrive on turnover and the arrival of new colleagues. Eva Frickel and Luiz Pedro de Carvalho joined NIMR in 2011 to set up new infectious disease research programmes, looking at Toxoplasma gondii and Mycobacterium tuberculosis, respectively.
Eva studied chemistry at the University of Freiburg, and then Biochemistry at Uppsala University. After a brief period in a protein crystallography lab in New Zealand, she obtained a PhD with Ari Helenius in Zurich, studying glycoprotein folding. This led her to think about protein degradation, and thereby antigen processing and presentation in the immune system. Eva then worked with Hidde Ploegh, at the Whitehead Institute at MIT, on immune surveillance of Toxoplasma gondii and the generation of parasite epitopes for recognition by CD8 T cells.
Once the parasite Toxoplasma gondii has infected a host cell it lives in its own vacuole that supposedly never fuses with lysosomes - the cellular organelle that usually clears exogenous pathogens. During infection, cells are known to produce gamma interferon. This cytokine is responsible for parasite control by activating factors restricting parasite replication or orchestrating killing of Toxoplasma. Lymphocytes called CD8 T cells confer resistance to the chronic phase of the parasite. The outcome of an infection with Toxoplasma is determined not only by the host's immune status, but also by the genotype and virulence of the infecting strain. It is unclear how Toxoplasma maintains the intricate balance between survival and host defense.
My work at NIMR continues my efforts to identify novel pathways and mechanisms of host resistance to Toxoplasma - how the vacuole of Toxoplasma is remodeled, not only to limit parasite replication, but also to facilitate Toxoplasma antigen presentation to exactly these CD8 T cells.
Eva’s work is supported by a Wellcome Trust Research Career Development Fellowship and a Wellcome-Beit Fellowship.
Luiz studied for a BSc and MSc from the Universidade Federal do Rio Grande do Sul, Brazil. He obtained his PhD in the laboratory of John S. Blanchard at the Albert Einstein College of Medicine, in New York, studying the biochemistry of essential mycobacterial enzymes. Luiz worked as a postdoctoral fellow in Carl Nathan’s laboratory at the Weill Cornell Medical College, working on the host interactions of Mycobacterium tuberculosis. In particular, he contributed to LC-MS-based metabolomics methods for systems-level studies of M. tuberculosis.
Mtb has evolved to survive inside the human macrophage, its sole natural reservoir. This extreme example of niche adaptation has re-shaped its genome, proteome and metabolome considerably. In addition to a very slow growth rate and considerably thick lipophilic cell wall, Mtb appears to not operate classic catabolite repression, making its eating habits quite unique among bacteria. In addition, Mtb does not produce a single toxin, so what kills the patient is its own immune response. Finally, Mtb is able to survive a variety of conditions and types of stress. In fact, it is likely that during active disease we Mtb experiencing considerably different phenotypic states.
At NIMR I will continue my metabolomics-based approach, combining mechanistic enzymology, molecular pharmacology and metabolomics in order to characterize Mtb’s lifestyle and creating and characterizing new drug candidates for the treatment of tuberculosis.
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