Stuart M. Krassner

Professor, Developmental & Cell Biology
School of Biological Sciences

Sc.D., The Johns Hopkins University, 1962

Phone: (949) 824-2801, 6542
Fax: (949) 824-4709

University of California, Irvine
4234, 4334 McGaugh Hall
Mail Code: 2300
Irvine, CA 92697

picture of Stuart M. Krassner

Morphological, metabolic, and biochemical analysis of developmental transitions (transformation) of hemoflagellates
The hemoflagellates are primitive parasitic protozoa that cause a number of diseases of medical and veterinary importance. One of these organisms, Trypanosoma cruzi, is the agent for Chagas Disease, the primary cause of heart disease in people under 40 in Central and South America. According to the World Health Organization, approximately 20 million people are infected with T. cruzi and another 90 million people are at risk from infection.

The life cycle of T. cruzi involves a vector insect host, triatomine bugs, and a number of vertebrate hosts. The developmental transition from one stage to another in these hosts is known as transformation. We are specifically interested in the transformation from the main insect stage, the epimastigote, to the vertebrate infective stage, the metacyclic trypomastigote. This developmental transition, which takes place in the insect hind gut, exhibits a number of fundamental changes in the molecular and cell biology of the parasite. These include changes in morphology, metabolism, infectivity for tissue culture cells as well as for vertebrate hosts resistance to complement mediated Iysis, qualitative and quantitative differences in intracellular and cell membrane protein patterns, and flagellar antigen reactive sites. Using a simple in vitro system we are studying the effects and mechanisms of action of a number of factors that induce or inhibit transformation from the epimastigote to the metacyclic trypomastigote stage (metacyclogenesis). These studies include analyses of the effects of small organic molecules (such as amino acids, sugars, and carboxylic acids), inorganic cations and anions, CO2 levels, organic metabolic and macromolecular inhibitors, and environmental factors (e.g., temperature, pH, and surface-to-volume ratios in culture vessels). As part of our studies we are attempting to define the main transition points during transformation to better understand the mechanisms involved in metacyclogenesis. A necessary, but not sufficient, reaction required for metacyclogenesis (both in vitro as well as in the insect vector) is cell-substrate adhesion prior to the developmental change. The window for adhesion appears to be sometime in G1, most probably before the restriction point for initiating the S phase. We are currently determining the kinetics of cell-substrate adhesion to better understand this phase of metacyclogenesis.

Another area of interest is related to the major metabolic shifts occurring during transformation. We hypothesize that cells shift from glycolytic catabolism during normal growth to Krebs Cycle-dependant aerobic catalysis of amino acids, particularly those involved in proline metabolism, during transformation. We are now testing the veracity of this hypothesis. Cells are harvested at different times during metacyclogenesis and analyzed using HPLC separation of cell extracts followed by fraction collection of free amino acid pools and cytoplasmic carboxylic acids.
Publications Krassner, S.M., J. Chang, S. Pak, K.O. Luc and B. Granger. 1993. Absence of transitory [Ca2+]; flux during early in vitro metacyclogenesis of Trypanosoma cruzi. J. Eukar. Microbiol. 40:224.
  Krassner, S.M., B. Granger, P. Lee, C. Guerra, T. Le and K.O. Luc. 1991. Action of exogenous potassium and calcium ions on in vitro metacyclogenesis in Trypanosoma cruzi. J. Protozoology 38:602.
  Krassner, S.M., B. Granger, P. Phermsangngam, T. Le and V. Linden. 1990. Further studies on substrates inducing metacyclogenesis in Trypanosoma cruzi. J. Protozoology 37:128.
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Last updated 08/03/2005