The MacLeod Group

Current Research

I work on single-celled parasites called African trypanosomes. African trypanosomes present a significant burden to large areas of sub-Saharan Africa, leading to an estimated $1.3 billion annual loss to the African economy. The majority of this economic cost is attributable to the veterinary disease Nagana, caused by the animal trypanosome species T. vivax, T. congolense and T. b. brucei. Nagana affects over 20 million livestock animals, lowering herd productivity and increasing mortality. This renders large areas of sub-Saharan Africa inhospitable for the more profitable livestock species and breeds. More directly, in humans, African trypanosomes cause the debilitating and often fatal disease African sleeping sickness, leading to a loss of 1.3 million disability-adjusted life years (DALY) to the African economy annually. The majority of trypanosome species are unable to infect humans due to an innate resistance mechanism. However, the T. brucei subspecies T. b. rhodesiense and T. b. gambiense have evolved to overcome this innate resistance and can infect humans. Of the two human-infective subspecies, T. b. gambiense is the more prevalent, causing more than 95% of human cases.

My research, funded by my Wellcome Trust senior fellowship, is focused on studying two main aspects of T.b. gambiense infections.

1. How the parasites cause infection?
2. How humans fight that infection?

How the parasites cause infection? T.b. gambiense is able to infect humans and cause severe disease while the highly related T.b. brucei subspecies is not? My group is using the latest molecular and sequencing technologies to determine the genes that vary in the parasite species to find out which of these genes are responsible for making some parasites able to infect humans. Recent breakthroughs include identifying mutations in two proteins that are crucial for T.b. gambiense to resist human innate immunity. By understanding the process of resistance to human innate immunity we can hopefully interfere with it and prevent disease.

How humans fight that infection? Some people are highly susceptible to trypanosomiasis, while others are asymptomatic or even resistant to infection. There is genetic variation in the host that contributes to the disease outcome. So we are using similar molecular techniques to find out the genetic differences in people that determine why they get more or less severe disease. In a similar way other animals that are resistant to infection by trypanosomes. By examining these animals and determining how they are resistant to infection, we can exploit their resistance mechanism to try to develop a treatment for the disease. 
To this end I have founded an international collaborative research network called TrypanoGEN. Funded by the Wellcome Trust as part of the H3Africa initiative, the overall aim of TrypanoGEN is to improve the health of people living in some of the poorest countries in the world which carry a disproportionate burden of infectious diseases. Despite their importance, the study of many tropical diseases has lagged behind that of diseases of developed countries. The TrypanoGEN network is redressing the balance by performing high quality research into human African trypanosomiasis. The data generated by this network will extend beyond trypanosomiasis susceptibility by providing a unique resource to study human genetic variation across Africa.

Research Group Members

Alexandra Raftery, PhD Student

Collaborations

TrypanoGEN has 4 main aims:

1 Generate a database of human genetic variation in different African countries and perform a genome-wide association study for susceptibility to trypanosomiasis. 
2 Create an extensive biobank housed in network hubs.
3. Develop infrastructure in African laboratories.
4. Provide training for African scientists.

More details about TrypanoGEN can be found at www.trypanogen.net

Parasite Street Science

Surge has developed a brand new street theatre show – Parasite Street Science – with Professor Annette MacLeod’s research group at the Wellcome Centre at the University of Glasgow which was presented at Surge Festival in Glasgow in July 2021. Continued funding will further develop the performance for Glasgow and Malawi.