Dr Sam Alsford
BSc MSc PhD
in Molecular Parasitology
I've been fascinated by parasite biology since carrying out two research projects on the surface biology of Schistosome blood flukes during my BSc at Imperial College. After completing an MSc in Molecular Biology of Infectious Diseases at LSHTM, I moved to Keith Gull's lab at the University of Manchester, where my PhD studies focused on gene expression and genome organisation in Trypanosoma brucei (the causative agent of human African trypanosomiasis and nagana in cattle, both devastating diseases).
In 2003, I returned to LSHTM, where I worked in David Horn's laboratory on several aspects of T. brucei molecular and cellular biology, including: epigenetics, and the control of gene expression and antigenic variation; molecular tool development and high-throughput phenotyping; and, understanding anti-trypanosomal drug uptake and intracellular transit.
In June 2012, following the award of a two year LSHTM/Wellcome Trust Institutional Strategic Support Fund Fellowship, I established my own laboratory and research programme at LSHTM (see below), further details of which can be found on my lab website.
I'm currently joint Head of the Doctoral College with Dr Alex Mold, having previously been Departmental Research Degrees Coordinator in the Department of Infection Biology (2014-2020) Faculty Research Degrees Director in the Faculty of Infectious and Tropical Diseases (2020-21).
I deliver lectures on the core Parasitology & Entomology (M3122) and Molecular Biology (M3333) modules in term-1. I organise Advanced Training in Molecular Biology (M3158) in term-2, delivering practical and bioinformatics classes, and several lectures. I also contribute to several other modules, including: Recombinant DNA Techniques (M3131) and Molecular Biology Research Applications & Progress (M3160) in term-2; and, Antimicrobial Chemotherapy (M3169) and Pathogen Genomics (M3460), which both run in term-3. More details can be found here.
I'm a tutor for the Medical Parasitology MSc programme, and serve on the programme committee and exam board.
Since June 2012, I've been pursuing my own research programme focusing on the interactions between Trypanosoma brucei and its host environment (more details can be found here). This work was initially funded by a two year LSHTM/Wellcome Trust Fellowship (2012-14), and subsequently a three-year project grant from the Medical Research Council (2013-2016).
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. 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 cel 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 here.