Intracellular parasitism is a type of symbiotic relationship in which the parasite benefits from a prolonged intimate association within its host cell. Toxoplasma gondii is an obligate intracellular parasite of the phylum Apicomplexa, which also includes the human and animal parasites of the genus Plasmodium, Eimeria and Cryptosporidium. Toxoplasma causes an opportunistic disease, toxoplasmosis, in individuals with immune dysfunction and in infected infants. Toxoplasma is uniquely adapted to the intracellular parasitism, being able to invade and survive in a wide range of cell types. Toxoplasma has retained 800 metabolic reactions during its evolution, contributing to its robust intracellular parasitism and wide host specificity.
The metabolic redundancy in central carbon metabolism of T. gondii allows us to investigate the fundamental principles governing the wiring of an intracellular and promiscuous parasite, and offers a novel perspective to pathogen–host interactions. The proposed research aims to construct a qualitative and quantitative model of the carbon metabolism of non-dividing (extracellular) and replicating (intracellular) parasites with quiescent and proliferative metabolic states, respectively. The project integrates the experimental and bioinformatic method to generate a model comprising the molecular interactions in a parasitized host cells.
The project involves biochemical and genetic analyses of proteins participating in bioenergetic pathways of the parasite (glycolysis, TCA cycle etc). The project includes in vitro parasite culture in human fibroblasts, fluorescence localization and genetic manipulation of parasite. The single- and double-deletion mutants of T. gondii shall be created and phenotyped. It is suitable for the students with a long-term carrier objective in the discipline of Infection Biology. For application and information please refer to the following references and/or contact the address below.
(1) Blume M, Contreras DR, Landfear S, Fleige T, Soldati DF, Lucius R, Gupta N; Host-derived glucose and its transporter in the obligate intracellular pathogen Toxoplasma gondii are dispensable by glutaminolysis: PNAS (2009) 106–31: 12998–3003
(2) Blume M, Hliscs M, Rodriguez-Contreras D, Sanchez M, Landfear S, Lucius R, Matuschewski K, Gupta N; A constitutive pan-hexose permease for the Plasmodium life cycle and transgenic models for screening of antimalarial analogs: FASEB J (2010) 25–4: 1218–29
Contact:
Dr Nishith Gupta (+49-30-2093-6404)
Principal Investigator
Department of Molecular Parasitology, Humboldt University
Philippstrasse 13, House 14, Berlin 10115
E-mail: Gupta.Nishith@staff.hu-berlin.de