Our lab aims to understand mitochondrial biogenesis,
metabolism and RNA processing in trypanosomatid protozoa, which are important parasites of man and livestock,
and to
utilize that knowledge to inform drug development.
In particular, our studies currently focus on the following three areas:
This project is aimed at shedding light on the essential - and
currently quite elusive - role that the mitochondrion plays in the
disease-causing (bloodstream) stage of trypanosomes. It also aims to
identify the adaptations that allow so-called dyskinetoplastic
trypanosomes to survive the loss of their mitochondrial genome, the
kinetoplast.
Trypanosome U insertion/deletion editing is a unique form of
post-transcriptional mRNA processing. It is catalyzed by a
macromolecular complex and of vital importance for the parasites. The
goal of this project is to determine the function of the various
editosome components, and how their activities are coordinated to
ensure precise editing.
One of the key components of the editosome is RNA editing
ligase 1
(REL1). As a postdoc in Ken
Stuart's lab Achim has shown that it is an essential enzyme
in the
disease-causing stage of Trypanosoma
brucei and, in collaboration with Wim
Hol's lab
at the University of Washington in Seattle, determined its
three-dimensional structure. We are now using high throughput
biochemical screens as well as in
silico methods to identify REL1 inhibitors that can serve
as
starting points for drug development.
Our lab is part of the Institute of Immunology & Infection
Research (IIIR)
and located on the 3rd floor of the Ashworth 3 building on
the
King's Building campus (click here for campus maps).
Click here for
contact info.
August 2018. Our paper on a mysterious connection between the trypanosome lysosome and mitochondrion now published in Antimicrobial Agents and Chemotherapy.
July 2018. Our paper on the function of mitochondrial DNA in transmission stage Trypanosoma brucei now published in PLoS Pathogens.
April 2018. Zan wins a poster prize at the British Society for Parasitology's Spring Meeting. Well done Zan!
January 2017. Our paper on the cryo-EM structure of the trypanosome ATP synthase complex now published in PNAS.
January 2017. Our paper on mitochondrial NADH dehydrogenases in T. brucei now published in MBP.
September 2015. Our paper on development of a high-throughput compatible activity assay for REL1 - an important step towards drug discovery - is now published in Nucleic Acids Research.
