WCAIR Deputy Director receives £2.1 million Wellcome Investigator award

Wellcome Centre for Anti-Infectives Research Principal Investigator and Deputy Director Professor David Horn will receive a £2.1 million Investigator Award from the Wellcome Trust. The award will allow David and his group to continue their research decoding gene expression mechanisms in trypanosomes, pathogenic protozoa that cause a range of human and animal diseases.

Professor Horn and his group study mechanisms that the Trypanosoma brucei parasite, and other trypanosomatid parasites, use to express virulence genes and adapt and survive in the hostile environments they encounter during their life cycles in insect and mammalian hosts. This understanding can lead to novel targets or pathways informing the development of new medicines for the treatment of sleeping sickness, Chagas disease and leishmaniasis.

Recent research highlights from the group include:

• Discovery of a regulatory ‘VEX’ protein complex that allows parasites to randomly switch on and off genes responsible for making the proteins covering the trypanosomes. The ability to change the type of surface protein is crucial to the parasites ability to survive attacks from the host defence system. Read more
• Discovery of a trypanosome regulatory protein complex that controls mitochondrial energy metabolism by specifically binding to a large group of RNAs encoding the so-called respiratome. Read more
• Demonstration that T. brucei is more metabolically flexible than previously thought and able to utilise both glucose and glycerol. This adaptability likely helps trypanosomes survive in different host environments. Read more
• Discovery of the target of a highly promising antitrypanosomal compound in advanced clinical trials; acoziborole targets cleavage and polyadenylation specificity factor 3. Read more
• Development of CRISPR-Cas9 system to allow precise genetic modification in T. brucei. Read more
• Demonstration of the major and underappreciated impact of DNA sequence, codon usage bias, on RNA and protein expression levels in trypanosomatid parasites. Read more

Professor Horn said, “I am hugely grateful to the Wellcome Trust, who have supported my research now for more than 20 years. I am also hugely proud of the achievements and successes of group members and other colleagues in recent years that helped to make this application successful; I consider myself very fortunate to be working with these people in Dundee.”

Professor Julian Blow, Dean of the School of Life Sciences, said “We have a long and proud record of working with Wellcome and turning their support into research that has a real impact in understanding, and ultimately treating, human and animal diseases.”

David received his first Wellcome Investigator Award on moving to Dundee in 2013. This provided a level of support and flexibility that allowed the team to develop projects with greater potential impact. Synergies with colleagues in the Mode of Action group and in the The Wellcome Centre for Anti-Infectives Research have substantially facilitated the application of new discoveries and technologies to advancing drug discovery efforts here in Dundee.