Trypanosomatid molecular & cellular biology researcher, molecular parasitology lecturer, and joint Head of Doctoral College @LSHTM.
Affiliations
Department of Infection Biology
Faculty of Infectious and Tropical Diseases
Centres
Antimicrobial Resistance Centre
Teaching
I deliver lectures on the core Parasitology & Entomology (M3122) and Molecular Biology (M3333) modules in term 1. I'm co-module organiser for Advanced Training in Molecular Biology (M3158) in term 2 (with Dr Rob Moon), delivering lectures, lab practicals and bioinformatics classes. I also contribute to several other modules, including: Recombinant DNA Techniques (M3131) and Molecular and Cell Biology of Infectious Diseases (M3260) in term 2; and, Antimicrobial Chemotherapy (M3169) in term 3. More details can be found at .
I'm a tutor for the Medical Parasitology MSc programme, and serve on the programme committee and exam board.
I'm joint Head of the Doctoral College with Prof Alex Mold (since August 2021), having spent one year as Faculty Research Degrees Director for ITD (2020-21) and six years as Departmental Research Degrees Coordinator for the department of Infection Biology (2014-2020).
I'm a tutor for the Medical Parasitology MSc programme, and serve on the programme committee and exam board.
I'm joint Head of the Doctoral College with Prof Alex Mold (since August 2021), having spent one year as Faculty Research Degrees Director for ITD (2020-21) and six years as Departmental Research Degrees Coordinator for the department of Infection Biology (2014-2020).
Research
My research programme focuses on the interactions between Trypanosoma brucei and its host environment (more details can be found at ).
I'm particularly interested in the uptake and intracellular transit of parasite- and host-derived molecules, such as nutrients, drugs and innate immune factors, and the genetic control of antigenic variation and ribosomal RNA transcription. My research is underpinned by a combination of high-throughput forward genetic screens and reverse genetic approaches, enabling the identification and characterisation of proteins involved in the uptake and intracellular transit of these molecules, as well as the parasite's response to them.
Using a high throughput genetic screen (Currier et al, 2018), we identified 63 parasite proteins that contribute to the trypanolytic action of apolipoprotein-L1 (the toxic component of human serum trypanolytic complexes), and we're now exploring their roles in apoL1 action, as well as broader T. brucei biology. Intriguingly, ten of our putative apoL1 sensitivity determinants have roles in dynamic ubiquitination and intracellular membrane trafficking.
We've also taken a similar approach to explore anti-leishmanial drug action (Collett et al, 2019), identifying a panel of candidate drug efficacy determinants in T. brucei, which is still a more tractable system than its fellow kinetoplastid parasite, Leishmania. We're now exploring their contribution to drug efficacy and their roles in T. brucei and Leishmania biology.
We've also applied this high throughput RNAi library approach to identifying the genetic determinants of RNA polymerase-I driven VSG monoallelic expression (Glover et al 2016; Davies et al 2021). By combining the RNAi library selection with a panel of bespoke rDNA locus reporter cell lines, we're now exploring the regulation of rRNA transcription and its intersection with VSG expression and differentiation.
The full range of plasmids for tagged protein expression and RNAi knockdown in T. brucei, developed in conjunction with David Horn, are freely available to the research community - details can be found at .
I'm particularly interested in the uptake and intracellular transit of parasite- and host-derived molecules, such as nutrients, drugs and innate immune factors, and the genetic control of antigenic variation and ribosomal RNA transcription. My research is underpinned by a combination of high-throughput forward genetic screens and reverse genetic approaches, enabling the identification and characterisation of proteins involved in the uptake and intracellular transit of these molecules, as well as the parasite's response to them.
Using a high throughput genetic screen (Currier et al, 2018), we identified 63 parasite proteins that contribute to the trypanolytic action of apolipoprotein-L1 (the toxic component of human serum trypanolytic complexes), and we're now exploring their roles in apoL1 action, as well as broader T. brucei biology. Intriguingly, ten of our putative apoL1 sensitivity determinants have roles in dynamic ubiquitination and intracellular membrane trafficking.
We've also taken a similar approach to explore anti-leishmanial drug action (Collett et al, 2019), identifying a panel of candidate drug efficacy determinants in T. brucei, which is still a more tractable system than its fellow kinetoplastid parasite, Leishmania. We're now exploring their contribution to drug efficacy and their roles in T. brucei and Leishmania biology.
We've also applied this high throughput RNAi library approach to identifying the genetic determinants of RNA polymerase-I driven VSG monoallelic expression (Glover et al 2016; Davies et al 2021). By combining the RNAi library selection with a panel of bespoke rDNA locus reporter cell lines, we're now exploring the regulation of rRNA transcription and its intersection with VSG expression and differentiation.
The full range of plasmids for tagged protein expression and RNAi knockdown in T. brucei, developed in conjunction with David Horn, are freely available to the research community - details can be found at .
Research Area
Chemotherapy
Drug discovery and development
Drug resistance
Innate immunity
Protozoa
Trypanosomes
Biochemistry
Bioinformatics
Cell biology
Genomics
Molecular biology
Parasitology
Disease and Health Conditions
African trypanosomiasis
Leishmaniasis
Neglected Tropical Diseases (NTDs)
Selected Publications
2021
Nucleic Acids Research
2019
Antimicrobial Agents and Chemotherapy
2018
PLoS pathogens
2017
FASEB journal
2016
Proceedings of the National Academy of Sciences of the United States of America
2014
PLoS pathogens
2012
Nucleic acids research
2012
Nature
2023
Journal of medicinal chemistry
2022
Heliyon