Dr Nicola Baker

Title: Making sense of how Leishmania detect changes in environmental pH

Abstract:

Parasites must continually respond to changing environmental cues for survival. Leishmania are a notable example, experiencing dynamic changes in pH within the sand fly vector, and again as they transition to and from the mammalian host. Leishmania must continuously sense and adapt to these changes throughout their life cycle to survive and cause disease. Orthology from other organisms (G-protein coupled receptors and receptor tyrosine kinases) is absent in Leishmania, and therefore little is known about how they sense and transmit these environmental cues, but protein kinases play an important role. A Leishmania protein kinase deletion library has identified a haptomonad-stage differentiation kinase (HDK1), required in early response to decreased pH. The haptomonad life cycle stage has a characteristic enlarged flagellar tip and is found attached within the sand fly but is rarely seen in cell culture conditions. Unusually, HDK1 mutants reversibly differentiate into the haptomonad life cycle stage in vitro upon pH reduction from 7.5 to 5.5. The HDK1 mutant can infect the midgut of a sand fly, but cannot attach to the stomodeal valve, thought to be important for onward transmission. Whole cell proteomics and RNAseq have revealed that cells undergo changes akin to AMPK activation as they differentiate into the haptomonad stage. They have also identified a second haptomonad differentiation kinase (HDK2) and some markers of the haptomonad life cycle stage. We are using proximity labelling to identify pathway interactors of HDK1 and aim to resolve this signalling pathway.


Bio:
Nicola is a Wellcome Trust fellow and group leader at the University of York. Her lab investigates the molecular mechanisms that allow Leishmania parasites to sense and adapt to their environment.
She began her career in parasitology at the London School of Hygiene and Tropical Medicine, earning her PhD in 2013 under the supervision of Prof. David Horn. Her doctoral research focused on drug resistance in African Trypanosomes. In 2017, she moved to the University of York to carry out postdoctoral research with Prof. Jeremy Mottram, shifting her focus to the role of protein kinases in Leishmania differentiation. This work laid the foundation for her independent career.

First published: 4 September 2025

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