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Dr Sam Alsford

BSc MSc PhD

Associate Professor
in Molecular Parasitology

Room
Lab 333 & Office 304B

LSHTM
Keppel Street
London
WC1E 7HT
United Kingdom

Tel.
020 7927 2352 (office) 020 7927 2699 (lab)

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 whole genome analysis; and, 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 web pages.

I can also be found at ResearchGate, Google Scholar and LinkedIn.

Affiliations

Faculty of Infectious and Tropical Diseases
Department of Infection Biology

Teaching

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.

After six years as Departmental Research Degrees Coordinator for the Department of Infection Biology (2014-2020), I took on the role of co-Research Degrees Director for the Faculty of Infectious and Tropical Diseases in September 2020.

Research

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've 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.

Previously, 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 various rDNA locus-integrated reporters, we're now exploring the regulation of rRNA transcription and its intersection with VSG expression.     

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.

Research Area
Drug discovery and development
Drug resistance
Innate immunity
Trypanosomes
Chemotherapy
Protozoa
Discipline
Genomics
Biochemistry
Cell biology
Molecular biology
Parasitology
Bioinformatics
Disease and Health Conditions
Leishmaniasis
African trypanosomiasis
Neglected Tropical Diseases (NTDs)

Selected Publications

TbSAP is a novel chromatin protein repressing metacyclic variant surface glycoprotein expression sites in bloodstream form Trypanosoma brucei.
Davies C; Ooi C-P; Sioutas G; Hall BS; Sidhu H; Butter F; Alsford S; Wickstead B; Rudenko G
2021
Nucleic Acids Research
Chemogenomic Profiling of Antileishmanial Efficacy and Resistance in the Related Kinetoplastid Parasite Trypanosoma brucei.
Collett CF; Kitson C; Baker N; Steele-Stallard HB; Santrot M-V; Hutchinson S; Horn D; Alsford S
2019
Antimicrobial Agents and Chemotherapy
Decoding the network of Trypanosoma brucei proteins that determines sensitivity to apolipoprotein-L1.
Currier RB; Cooper A; Burrell-Saward H; MacLeod A; Alsford S
2018
PLoS pathogens
Ornithine uptake and the modulation of drug sensitivity in Trypanosoma brucei.
Macedo JP; Currier RB; Wirdnam C; Horn D; Alsford S; Rentsch D
2017
FASEB journal
VEX1 controls the allelic exclusion required for antigenic variation in trypanosomes.
Glover L; Hutchinson S; Alsford S; Horn D
2016
Proceedings of the National Academy of Sciences of the United States of America
Cathepsin-L can resist lysis by human serum in Trypanosoma brucei brucei.
Alsford S; Currier RB; Guerra-Assunção JA; Clark TG; Horn D
2014
PLoS pathogens
High-throughput decoding of antitrypanosomal drug efficacy and resistance.
Alsford S; Eckert S; Baker N; Glover L; Sanchez-Flores A; Leung KF; Turner DJ; Field MC; Berriman M; Horn D
2012
Nature
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