The development of an invertebrate worm model for the discovery of new synergistic drug combinations for the treatment of snakebite envenoming

Kofi Annan called snakebite “The biggest public health crisis you’ve never heard of”. Snakebite envenoming is a medical emergency that is estimated to kill over 100,000 victims every year and maim a further 400,000. Current treatments, conventional antivenoms, are expensive, unstable at warm temperatures, and require intravenous administration. Unfortunately, it takes an average of 4-9 hours for a snakebite victim to reach hospital for antivenom treatment, during which time severe damage or even death may have already occurred. New point-of-care treatments that could be carried on one’s person and administered within minutes of being bitten, thus buying the victim time to reach hospital for further treatment, are desperately needed.

Small molecule drugs (think of paracetamol or antibiotics) that inhibit specific snake venom toxins are one possible solution. As a pharmacology and snakebite laboratory, we are interested in studying the activity of drugs as inhibitors of snake venoms. We are particularly interested in elucidating novel combinations of drugs that may synergistically (that is, the overall activity of the drug combination is greater than the simple sum of their parts) inhibit the toxic activity of snake venoms from multiple species from around the world, with the goal of developing a pan-species effective therapy that could be used globally to treat snakebite victims.

This work will largely occur within cell-based assays, determining which combinations best inhibit the venoms’ toxic activity against human cell lines. However, it can be difficult to jump to more robust and ethically more contentious animal studies from such data. Therefore, the second part of this project will be to develop an invertebrate worm model of envenoming using Lumbriculus variegatus, which will provide a more robust model of envenoming than simple cellular assays without delving into vertebrate animal experiments. The final experiments within this PhD will be to determine the pan-species potency and efficacy of the cell-optimised drug combination therapies in the L. variegatus model to evidence its potential utility as a future treatment of snakebite envenoming.

Snakebite is a devastating neglected tropical disease that continues to destroy lives and families, even in survivors who may be left with permanent injuries that drastically impact their livelihoods and personal lives. We are trying to reduce this impact. The successful applicant to this PhD studentship has the chance to work at the forefront of this exciting and rapidly evolving field and to complete research that could help improve and save the lives of thousands of snakebite victims in the years to come.

Applicants should hold a minimum upper second-class honours degree in pharmacology, biochemistry, cell biology, or a related discipline. A Masters degree is desirable.

For informal discussions and queries in advance of applying, please contact Dr Steve Hall ([email protected]).

To apply, please send your CV (max 2 pages) including the names of two referees and cover letter (outlining your interest in this PhD and qualifications) to Dr Steve Hall ([email protected])