Current Projects
Elucidating the Import Machinery in Glycosomes
Biochemical fractionations and superresolution microscopy reveal that glycosome composition is heterogeneous. We hypothesize that this heterogeneity is a consequence of the biogenesis process and functional specialization according to metabolic capabilities. We are using organelle flow cytometry to define different glycosome populations. In addition, we are also working to resolve the roles that post-translational modifications of the import machinery play in protein import.
Decoding the Glycosome Import Complex
Matrix protein import involves several membrane complexes comprised minimally of Pex13.1, Pex13.2 and Pex14. We are working to resolve the protein composition of these import complexes, define the residues that mediate their interactions, and determine how the post-translational modifications of import components influence protein import.
Clemson University Investors (INclusiVe Excellence in Science and Technology)
Meredith Morris Lab
Overview of Our Research
Trypanosoma brucei harbors essential, highly specialized organelles called glycosomes. Our lab is focused on resolving the molecular mechanisms that regulate glycosome homeostasis, which involves the coordination of multiple processes including:
organelle formation from the endoplasmic reticulum and subsequent import of membrane and matrix proteins
protein import
organelle proliferation via fission of existing organelle
specialization of glycosome composition according to metabolic function
degradation/recycling of glycosomes via autophagy
Protein import is a highly conserved process mediated by one of two pathways. Both pathways involve soluble receptors that bind sequences in the protein bound for the glycosome. In PTS1 import, the soluble receptor Pex5 binds a C-terminal tripeptide-- typically SKL. In PTS2 import, the soluble receptor Pex7 binds an N-terminal sequence. Both PTS1 and PTS2-receptor:cargo complexes dock at the import channel involving the membrane proteins Pex13 and Pex14. Trypanosomes are the only organisms that have two Pex13s (Pex13.1 and Pex13.2); both of which are essential. We are working to define the functional differences between the two Pex13s and identify ways to inhibit their function. Disruption of these pathways is lethal to parasites.