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Dr Sam Alsford

Associate Professor

United Kingdom

Tel.
+44 (0) 207 927 2352

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 http://blogs.lshtm.ac.uk/alsfordlab/teaching/.

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 Dr 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 http://blogs.lshtm.ac.uk/alsfordlab/research/).

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 http://blogs.lshtm.ac.uk/alsfordlab/cell-lines-plasmids/.

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

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
Bis-6-amidino-benzothiazole Derivative that Cures Experimental Stage 1 African Trypanosomiasis with a Single Dose.
Racané, L; Ptiček, L; Kostrun, S; Raić-Malić, S; TAYLOR, MC; DELVES, M; ALSFORD, S; Olmo, F; FRANCISCO, AF; KELLY, JM;
2023
Journal of medicinal chemistry
Synthetic biology tools for engineering Goodwin oscillation in Trypanosoma brucei brucei.
Borg, Y; ALSFORD, S; Pavlika, V; Zaikin, A; Nesbeth, DN;
2022
Heliyon
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