The McMorran Group - Genetics and Infectious Diseases

Genetics and Infectious Diseases

The main focus of our research is to understand the host response to malarial infection. Malaria survival has been a major driver in the evolutionary history of humans and many protective mechanisms have arisen that determine an individuals’ susceptibility to infection. We are interested in discovering novel genes and pathways that protect the host during an infection, and using this knowledge to develop so-called host-directed therapies for malaria.

About malaria

Malaria is caused by the Plasmodium parasite, which is transmitted between people by mosquitoes, and infects the liver and red blood cells; clinical symptoms arise during the erythrocytic stage. Infections can result in flu-like symptoms and periodic fevers, which if unchecked, increase in severity and can further develop into serious life-threatening conditions, including severe anaemia, respiratory distress and coma. Millions of people living in the tropics are at risk of infection and young children, particularly those living in Africa, are most susceptible; the disease kills at least 1 million people each year. The widespread development of drug-resistant parasites is hampering ongoing control and elimination programs, motivating urgency for new ways to combat the disease.

A hosted-directed approach to malarial treatment

Critical to an individual’s ability to survive an infection are the genetic makeup and ability to mount an appropriate protective response. Several genetic polymorphisms are associated with increased resistance to malarial infection, and these polymorphisms are common in populations living in malaria endemic regions. Compared to the short effective half-lives of modern antimalarial drugs, genetic-based protection, which has arisen through natural selection, has provided protection for millennia. This is because the anti-malarial effects are outside the genetic control of the parasite, whereas all current drugs target parasite molecules; variant parasite strains that modify the drug or mutate its target protein can (and have) rapidly arisen through their own selective bottlenecks. We propose that drugs that mimic host genetic-based protection will be highly effective and resistance-proof antimalarial agents. We call this approach host-directed therapy.

Updated:  25 September 2018/Responsible Officer:  Director, JCSMR/Page Contact:  Web Manager