Dr Colin Sutherland
BSc PhD MPH
Colin is a biologist and parasitologist who joined the School in January 1998 to work as a Post-Doc with Professor Geoffrey Targett on the gametocytes of Plasmodium falciparum. Colin began working on parasite drug resistance in the context of the team's clinical studies in The Gambia from 1998 - 2002. From 2004 - 2011, while continuing his studies of parasite drug susceptibility, Colin developed new projects on molecular diagnostics for parasitology with Peter Chiodini and Spencer Polley in the Department of Clinical Parasitology at the Hospital for Tropical Diseases, and continues to work closely with Public Health England in the PHE Malaria Reference Laboratory, LSHTM as HCPC-registered Clinical Scientist.
Understandng of the evolutionary biology of parasitism remains the context underpinning all Colin's studies, and the tools of molecular genetics and genomics are the means used to address this goal. Parasite adaptation to the two great selective forces of host immunity and antimicrobial chemotherapy has been of particular interest.
Among Colin's current roles are:
- Editorial Board Member for the Journal of Antimicrobial Chemotherapy
- Member of the Grants Committee for the British Society for Antimicrobial Chemotherapy
Colin contributes lectures to students studying for MSc degrees and the DTM&H. He has supervised more than 30 MSc summer research projects in the laboratory.
Colin's lab group has been involved in training researchers from a number of malaria endemic countries in techniques for molecular genotyping of malaria parasites. Trainees and students have hailed from Burkina Faso, Chad, China, Guinea-Conakry, Indonesia, Kenya, Mali, Niger, Nigeria, Pakistan, The Philippines, Senegal, Sudan, Tanzania, Thailand and The Gambia, and include scientists, clinicians, doctoral students and research assistants.
Colin also contributes to a number of PhD examinations each year. Recent candidates have included students from the Universities of Keele, Oxford and Liverpool.
Recently completed doctoral students:
Ifeyinwa Chijioke-Nwauche (Nigeria) - "Efficacy of artemether-lumefantrine and resistance marker selection in HIV positive and negative adults in southern Nigeria."
Completed: January 2014
Gisela Henriques (Portugal) - "New genetic markers of artemisinin resistance in human malaria parasites."
Completed: June 2015
Mary Grace Dacuma (The Philippines) - "Epidemiology of malaria in the provinces of Sarangani, South Cotabato and Tawi-Tawi in Mindanao, The Philippines "
Completed: June 2015
Ifeyinwa Aniebo (Nigeria) - "Genomic approaches to understanding drug resistant phenotypes in Plasmodium falciparum "
Completed: June 2017
Inke Nadia Lubis (Indonesia) - "Clinical efficacy of artemisinin-based combination therapy for uncomplicated Plasmodium falciparum malaria in North Sumatera, Indonesia, and the association of molecular markers with treatment outcomes"
Completed: Jan 2018
Current PhD candidates:
Ryan Henrici (USA) - "Manipulation of artemisinin susceptibility in African malaria parasites by genome editing"
Expected completion: June 2018
Fiona Shilliday (UK - joint student with Birkbeck) - "Members of the kinesin-8 and -13 motor families in P. falciparum: their putative roles in parasite cell division and potential as novel anti-malarial drug targets"
Expected completion: Autumn 2019
Colin's research falls into 3 main areas: Plasmodium falciparum gametocyte biology, malaria drug resistance and molecular diagnostics for malaria infections. The following projects are currently active in the lab:
1) Drug resistant genotypes associated with reduced susceptibility of African P. falciparum
Earlier work with Teun Bousema evaluated combination antimalarials containing artemisinin compounds, and the genetic determinants of susceptibility to these regimens in malaria parasites. This work was funded by the EU-FP7 MALACTRES consortium from 2008 until June 2013. The lab continues to work with collaborators running a number of trials and studies throughout Africa in which ACT efficacy is tested.
Through the work with Dr Bousema in western Kenya, we have identified mutations in the P. falciparum genes, pfubp1 and pfap2mu that are associated with reduced susceptibility to ACT in vivo. We have expanded these studies to include a small focus of ACT treatment failures in Masaiti Disctrict, Zambia. Our data from both sites clearly show that determinants of susceptibility in Africa differ from those recently described in Cambodia.
With funding from the British Society for Antimicrobial Chemotherapy, we have generated transgenic P. falciparum to examine the role of polymorphisms in the pfap2mu locus in modulating parasite response to antimalarial drugs in vitro.
2) New molecular tools for diagnosis of parasitic infections
Public Health England is supporting the development of new DNA amplification assays both in the Malaria Reference Laboratory at LSHTM, with Dr Debbie Nolder and Paul Lansdell, and with Dr Spencer Polley and Prof. Peter Chiodini at the Hospital for Tropical Diseases (HTD). New real-time qPCR assays for Plasmodium falciparum, P. vivax and P. ovale spp. have been developed and have entered routine diagnostic use. These quantitative assays are also being used to monitor parasite clearance times in patients under treatment in HTD.
In addition, clinical evaluation of LAMP technology for malaria diagnosis developed with Spencer Polley at the Clinical Parasitology Dept at HTD with funding support from FIND, Geneva were described in the Journal of Infectious Diseases in June 2013. A MESA-funded project with Dr Mary Grace Dacuma supported us to take this technology to South Cotabato Province, Mindanao, The Philippines in 2015 and demonstrated its utility in remote field settings.
3) Population biology of P. ovale curtisi and P. ovale wallikeri
Dr Mary Oguike has lead the work on these two distinct forms of malaria parasite, first described in 2010 as part of Colin's work in the UK Malaria Reference Laboratory, and successfully generated Ilumina paired-end genome seq data direct from blood samples from patients with ovale malaria. Together with Prof Abdoulaye Djimde, University of Bamako, Mali we continued new genomic analyses, and studies of the liver-stage biology of these two species with Medical Research Council funding from 2013-16. With the assistance of Mojca Kristan and Dr Don van Schalkwyk we have developed a mosquito transmission pipeline, and in 2016 successfully infected cultured human hepatocytes with sporozoites from P. ovale spp.
4) In vitro drug responses of parasites isolated from UK malaria patients
As Clinical Scientist at HTD, Colin has direct contact with malaria patients who have returned to or visited the UK from malaria-endemic countries. Dr Don van Schalkwyk and Rebekah Burrow successfully adapted more than 10 P. falciparum isolates from across Africa to long-term in vitro growth since 2012, and we are now using these for further dissection of parasite susceptibility to a variety of antimalarial drugs in vitro. Ifeyinwa Aniebo has generated full genome sequence in-house (on the Illumina Mi-Seq platform at LSHTM) for some of these isolates. Ryan Henrici has successfully exploited CRISPR-Cas9 genome editing to demonstrate the importance of polymrphisms in candidate genes pfubp1 and pfap2mu in modulating artemisinin susceptibility in vitro.
In January 2017 we published a case series of four malaria patients that experienced recurrent malaria symptoms 3-7 weeks after treatment with artemether-lumefantrine, the front-line antimalarial in the UK. This report, which inlcuded genetic analysis of several candidate resistance loci, generated significant media interest at the time of publication.
5) In vitro drug suscetibility of P. knowlesi
The Medicines for Malaria Venture (MMV) are supporting a project with Don van Schalkwyk, together with the lab of LSHTM colleague Dr Robert Moon, in whcih we have successfully established robust in vitro susceptibility assays for the zoonotic parasite P. knowlesi. We have used this to screen investigational lead compounds for activity against non-falciparum malaria, and to identify differences in the drug susceptibility of this species compared to the more familiar P. falciparum.
6) EDCTP-funded studies of ACT therapy for children with malaria in West Africa
This project, coordinated by Prof Djimde in Bamako, brought a number of European and African project partners together to design. implement and evaluate Phase III trials of ACT therapies in Mali, Burkina Faso and Guinea-Conakry. Particularly exciting is the opportunity to be involved in the first large-scale trials of artesunate-pyronaridine for treating malaria in African malaria patients. Khalid Beshir developed a novel qPCR method for evaluating parasite clearance in malaria patients to be deployed across this project. Colin is involved in preparation of several manuscripts from this work for submission in 2017.
7) ACCESS-SMC - monitoring and evaluation of parasite drug resistance
As part of this UNITAID implementation project, being carried out on a vast scale across 7 Sahel countries in the seasonal malaria belt in Africa, Khalid Beshir and Julian Muwanguzi are performing high-throughput parasite detection and assessment of resistance markers for the combination of drugs used for seaonal malaria chemoprevention (SMC) in young children - sulphadoxine-pyrimethamine plus amodiaquine. The team have established an ingenious analysis pipeline, starting with the collection of bar-coded filter-paper blood-spots from ~4000 children in each participating country, followed by robotic DNA extraction of DNA at LSHTM, qPCR to test for parasites and finally sequencing of key parasite resistance loci in parasite positive samples.