Lifecycle control in trypanosomes - Keith Matthews

The Trypanosoma are group of unicellular parasitic flagellate protozoa species.  In people they cause Human African Trypanosomiasis, or sleeping sickness, which until recently killed thousands of people annually.  Trypanosomes continue to inflict significant disease in animals, in particular causing the cattle diseases nagana with huge economic impact in affected regions of sub-Saharan Africa.

The question of lifecycle control in trypanosomes is very accessible to molecular cell biology: parasites  at different lifecycle stages can be cultured in vitro, they can be genetically transformed, gene transcripts can be ablated by RNA interference and differentiation between life stages is simple and reproducible.

The trypanosome life cycle involves progression of a proliferative cell (e.g. a stem cell) into cell-cycle arrest, this being followed by cell specialization via differentiation - proliferative cells (bloodstream slender forms) undergo cell cycle arrest in response to an autocrine signal, after which the arrested cells (stumpy forms) differentiate in response to environmental cues to produce a new differentiated (but proliferative) cell type (procyclic cells).

The genome sequence of these parasites has now been completed, revealing that ~60% of  trypanosome genes are not found in other organisms.  It is these genes that may provide the keys to understanding the unique and interesting biology of trypanosomes.

In addition to identifying novel mechanisms for the control of sleeping sickness in both humans and animals, work in the Matthews also represents a model for eukaryotic cell differentiation which can unlock conserved processes fundamental across eukaryotic cell biology.