Page 14 - LSTM_AnnualReport1415

FEATURE ARTICLE:

Resistance research &

management

LSTM was among the rst institutions to recognise the importance

of studying and understanding the phenomenon of drug resistance.

Pioneers such as Professor Warrington Yorke, the rst Walter Myers

Chair of Parasitology, established in 1929 an in vitro cultivation of drug

resistant trypanosomes in order to understand how new drugs work.

Many factors drive resistance, and in recognition of this LSTM The Department of Vector Biology is leading the search
has developed an interdisciplinary approach involving the for the molecular mechanisms underpinning resistance

entire research continuum from bench, to clinical care, to to insecticides used against the Anopheles mosquitoes
public health and policy. This involves specialist teams of that transmit the disease. Using techniques including

laboratory scientists, engineers, mathematical modellers, microarray, RNAseq, association mapping, metabolomics and
clinicians, public health specialists and social scientists transgenesis, researchers have identi ed the major genes

working together within and across traditional disciplinary responsible for resistance to the key classes of insecticides
boundaries. LSTM’s continued commitment to this used to control malaria vectors. This is being used to identify
important area of research is evident from our institutional patterns of cross resistance, develop diagnostics and plan

strategy to use recent Wellcome Trust ISSF funding to drive insecticide resistance management programmes. Members
appointments and projects in this area.
of the Vector Biology department are working closely with

industry to incorporate this knowledge into the design of
Understanding resistance at the molecular level
new insecticides. Some of their ndings were presented

LSTM scientists have helped to unravel the mechanisms of during an ‘Industry Day’ in July 2015.

resistance in malaria parasites and in the mosquito vector. At the genetic level, LSTM is driving the Anopheles gambiae
Parasitologists have helped nd what causes resistance to 1000 genomes project, in collaboration with the Wellcome
chloroquine, Fansidar and atovaquone. Recently we have
Trust Sanger Institute. The exploration of this rich data set is
been working on studies to understand resistance to new providing new clues about the selection process resulting in
antimalarials, the artemisinins, which represent the last line
insecticide resistance.
of defence against the malaria parasite. Resistance is already
emerging in South East Asia, which may impact substantially Accelerating the development of new drugs

on attempts to eliminate malaria worldwide.
Drug discovery has been a cornerstone of LSTM activities
throughout its history. As early as in 1905 LSTM sta
were establishing the e ectiveness of the arsenical agent

Atoxyl against African Trypanosomiasis. By 1921 the rst
clinical studies with Suramin were initiated and by 1927

Chemotherapy was established as a core subject by Yorke,
Adams and Murgatroyd in LSTM.

The rst demonstration of
acquired resistance to an
antimalarial drug was

reported by Fulton and
Yorke working with
RESEARCH CENTRE FOR
Plasmodium knowlesi.
DRUGS & DIAGNOSTICS
Throughout the 40s and
50s LSTM was at the centre of studies to develop

chemotherapeutic agents active against, malaria,
trypanosomiasis and scabies.
Trophozoites

14