Self funded MSc by research or PhD in Biology: Paratransgenesis for leishmania

Lead supervisor: Dr D Jeffares (Dept of Biology)

Co-Supervisor: Dr Sean Meaden and Dr Paul Fogg (Dept of Biology)

The student will be registered with the Department of Biology

Leishmaniasis is an infectious disease caused by protozoans of the Leishmania clade that are transmitted by sand flies. About 700 000 to one million new cases of leishmaniasis occur each year. There are three main forms of the disease; cutaneous leishmaniasis (where the parasite causes disfiguring skin ulcers), mucocutaneous (where the parasite causes destruction of tissues around the mouth, nose or throat) and visceral leishmaniasis (where the parasite enters the spleen and bone marrow). Visceral leishmaniasis is almost always fatal without treatment. Leishmaniasis primarily affects the poorest people within Africa, Middle East, Central Asia and South America.The association of leishmaniasis with poverty poses considerable challenges to diagnosis, control of parasites and treatments. There is no vaccine for leishmaniasis. There are very few drug treatments available, and all the current drugs have terrible shortcomings.

Paratransgenesis may be the solution. Paratransgenesis is a technique to introduce a genetically engineered bacteria into a vector (such as a sandfly) that kills the parasite. Because leishmania parasites are only transmitted by sand flies, if we could stop or reduce transmission, we might be able to limit the occurrence of new cases. Imagine a bacterial species that persists within the gut of a sandfly that transmits Leishmania, and can be cultured and transformed as easily. Potential bacteria have been discovered (Vaselek et al. 2024); if we could engineer these to produce peptides that are known kill Leishmania cells (Hagemann, Macedo, and Tasca 2024) when it is in a sandfly (but not in other conditions) the cycle of transmission could be broken entirely.

The advantage of the paratransgenesis approach over existing methods (drugs, vaccines) is that the antileishmanial substance grows and persists within the sandfly. For Leishmania species that are primarily maintained within human hosts (anthroponotic), introducing such a bacteria wherever human cases are occurring may break the cycle of transmission. This is where we want to get to.

This project will advance the technology towards the practical use of paratransgenesis to reduce the transmission of leishmaniasis. This has potential to have a considerable impact on human health. The project will involve some/all of (depending on the student); developing the tools to engineer bacteria that are known to infect the intestinal tracts of sand flies, study of the gene expression systems of these bacteria, study of the microbiomes of sand flies through their lifecycle and/or studies of the efficacy of anti-leishmanial peptides. Many of these approaches will involve training in the use of next generation sequencing using bioinformatics approaches. The supervisors have extensive contacts with researchers in Africa and South America, so field trips to such locations would be encouraged.

Hagemann, Corina Lobato, Alexandre José Macedo, and Tiana Tasca. 2024. “Therapeutic Potential of Antimicrobial Peptides against Pathogenic Protozoa.” Parasitology Research 123 (2): 122. Vaselek, Slavica, Basak Ezgi Sarac, Ali Doruk Uzunkaya, Ayda Yilmaz, Cagatay Karaaslan, and Bulent Alten. 2024. “Identification of Ochrobactrum as a Bacteria with Transstadial Transmission and Potential for Application in Paratransgenic Control of Leishmaniasis.” Parasitology Research 123 (1): 82.

The Department of Biology is ranked in the top 10 overall in the UK for research excellence according to the Times Higher Education ranking of the latest REF results. We are committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills. We’re exceptionally proud to have held an Athena SWAN Gold award since 2014 in recognition of our commitment.

Programme: MSc by Research in Biology (1 year) or PhD in Biology (3 years)

Start Date: 16th September 2024. 

We would encourage candidates to email the project supervisors a 2-page academic CV to discuss their suitability for the project before applying.

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