Jim Morris Lab

Overview of Our Research

The J. Morris lab has two areas of interest, both centered around glucose metabolism.  The first is focused on African trypanosomes while the second centers on pathogenic free-living amoebae. 

Glucose perception and regulation of development in the African trypanosome.  Parasites that have developmental stages in distinct hosts encounter remarkably different environments during their lifecycles. For example, parasite members of the family Trypanosomatidae, including the African and American trypanosomes and Leishmania spp., have required lifecycle stages in both insect vector and mammalian host. These parasites have evolved distinct mechanisms to avoid eradication by the host immune system. In common, however, is the requirement that these parasites must be able to identify the host in which they reside and respond accordingly. The African trypanosome, Trypanosoma brucei, responds to changes in environmental glucose availability to regulate developmental progression. While in the mammalian blood, the parasite is bathed in glucose at a nearly constant concentration (~5 mM). Shortly after ingestion by a feeding tsetse fly, the blood sugar is depleted, triggering a developmental program in the parasite. While glucose sensing is not unique to T. brucei (pancreatic cells respond to blood glucose levels by the release of insulin in order to maintain homeostasis in mammals), the parasites have evolved the means to “sense” dramatic changes in the environment (from mammal to insect). Our group is interested in elucidating the molecular mechanisms employed by the African trypanosome to detect glucose availability, with a particular focus on identifying unique components for targeting for therapeutics. Rationale: The parasitic members of the family Trypanosomatidae infect ~32 million people worldwide. The lack of effective therapies for these maladies emphasizes the need for the identification of new targets for drug development. Our research focuses on identifying for the development of therapies the mechanisms that the African trypanosome uses to “sense” its environment and make developmental decisions.

Carbon metabolism in the pathogenic free-living amoebae.  Our group also works to understand the contributions of glucose metabolism to amoebae known to cause human infections that are found ubiquitously in the environment.  These amoebae, including Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba spp., are all capable of causing devastating illnesses – with brain infections by the first two being nearly uniformly fatal.  We have found that these parasites all harbor a single enzyme, a glucokinase, capable of phosphorylating glucose, which is a key early step in both glycolysis and nucleotide biosynthesis.  We have found differences in parasite and human host glucokinases, and are working to exploit these findings to develop desperately needed new therapeutics.