Besides causing significant disease, parasites are some of the most ancient eukaryotes (cells with a nucleus). Using comparative genomics and experimental cell biology, the Field lab explores how eukaryotes have evolved and changed over time. Eukaryotes have a fundamental characteristic in common- they organise the contents of their cell into compartments. We use trypanosomes as a model to understand how these compartments are formed (Read paper).

Trypanosomes are unique among single-celled organisms in that they have a single entry/exit point across which nutrients and wastes are traded with their environment. This means we can use Trypanosomes to observe this process of transport of molecules within the cell. This process plays important roles in drug sensitivity and severity of infection (Read paper).
By understanding how drugs interact with parasites, we can design more potent molecules.

One compartment we are especially interested in is the nucleus. The components of the outer edge of the nucleus, including the pores in the nuclear membrane and proteins called lamins, create a complex architecture. It is dramatically different from the human nucleus. Interestingly, the structure plays pivotal roles beyond defining the shape of this organelle. It also directly interacts with the parasite genome and is involved in gene expression (Read paper).

The Field lab uses genetics and proteomics to identify novel components of the nuclear architecture and discover how they contribute to the severity of parasite infections. Components that are unique to the parasite (not found in humans) and required for survival are great starting points for drug discovery.

Conservation and divergence at the nuclear envelope. The major protein and nucleic acid complexes responsible for control of gene expression, nucleocytoplasmic transport, and regulation of nuclear architecture are shown.
Conservation and divergence at the nuclear envelope. The major protein and nucleic acid complexes responsible for control of gene expression, nucleocytoplasmic transport, and regulation of nuclear architecture are shown. From Rout MP, Obado SO, Schenkman S, Field MC (2017) Specialising the parasite nucleus: Pores, lamins, chromatin, and diversity. PLoS Pathog 13(3): e1006170. https://doi.org/10.1371/journal.ppat.1006170