ERC Starting Grant for Tom Beneke: Drug resistance in tropical parasites
University of Würzburg
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Dr Tom Beneke in his lab. The Würzburg researcher has been awarded a grant worth 1,5 millions from the European Research Council for his work on the tropical parasite leishmania.
view moreCredit: Robert Emmerich / University of Würzburg
Through its Starting Grants, the European Research Council (ERC) supports talented early-career researchers who can demonstrate an outstanding track record and an excellent new research idea.
This is precisely the case for molecular biologist Dr Tom Beneke (35) from the Biozentrum at the University of Würzburg. The ERC has awarded him one of its €1.5 million grants to further advance his research on Leishmania and the disease they cause.
This is yet another great success for the scientist. Just a few weeks ago, the German Research Foundation (DFG) awarded him 2.2 million euros to set up a junior research group. This project also focuses on Leishmania parasites.
“The ERC Starting Grant is a fantastic recognition of our work to date. Together with the recently awarded Emmy Noether grant and other externally funded projects, we can now establish a long-term research programme in Würzburg and investigate key questions about Leishmania biology and the causes of treatment failure in leishmaniasis,” says Tom Beneke.
Drug resistance is on the rise
Leishmania parasites are also found around the Mediterranean. They are transmitted to humans, as well as to dogs and other animals, through the bites of sand flies. Some Leishmania species cause skin ulcers, whilst others mainly affect the liver and spleen – the latter is almost always fatal if left untreated. Every year, up to one million people worldwide develop leishmaniasis, and several thousand die from the disease.
There are no approved vaccines for humans, and the available treatments often cause severe side effects. At the same time, resistance to the few available drugs is increasing.
Parasites can enter a dormant state
In his ERC project ‘PERSIST’, Tom Beneke is investigating the parasites’ drug resistance. Some evade treatment by entering a kind of dormant state inside their host cells. Researchers refer to this as persistence. In this state, the pathogens grow only very slowly or not at all – which makes them even more difficult to target with drugs. As soon as treatment ends or the effect of the drugs wears off, the Leishmania parasites can become active again.
For a long time, researchers regarded this dormant state as a temporary reaction by the parasites to stress caused by the drugs. “However, recent research findings, including those from my group, suggest that certain genetic variations increase the likelihood of the parasites entering a state of persistence,” says Tom Beneke.
Unravelling the genetics of the pathogens
The Würzburg-based researcher aims to identify which Leishmania genes control the switch between active and dormant states in the parasite. He also wishes to clarify whether Leishmania possess a kind of biological memory that makes them particularly prone to repeatedly entering a dormant state. In addition, research will focus on how these mechanisms differ from classic resistance mutations and which genetic changes make Leishmania more susceptible to drugs.
The findings could help to significantly improve the treatment of leishmaniasis. The long-term aim is to develop new combination therapies that not only combat resistance but also prevent the formation of surviving dormant stages, thereby reducing relapses following treatment.
Tom Beneke’s career
Tom Beneke, born in 1990, is from Berlin and studied biotechnology at the Brandenburg University of Technology Cottbus-Senftenberg. After completing his bachelor’s degree, he moved directly to the University of Oxford as part of a fast-track PhD programme without first completing a master’s degree. There, he completed his PhD between 2015 and 2019, focusing on the swimming behaviour of Leishmania parasites.
Beneke then continued his research in Oxford for a short period of time before subsequently moving to the biotech company Oxford Genetics as a specialist in CRISPR screening. However, after just under two years in industry, he decided to return to academic research. In 2022, he joined the Biocentre at the University of Würzburg on fellowships from the European Molecular Biology Organisation (EMBO) and the European Union (Marie Curie). Here, he continued his research on Leishmania.
In 2024, he established an independent junior research group. In addition to the Emmy Noether Programme, this group is funded by further third-party projects. These include another DFG grant, a Horizon Europe project and a grant from the Humboldt Foundation.
A University of Stirling study could pave the way for the more efficient study of the secretions that salmon lice use to avoid fish defences, potentially enabling the development of new strategies to protect salmon from infestations. Research led by PhD
Salmon lice feed on the skin, mucus, and blood of fish, causing open wounds that can lead to infection – reducing the market value of farmed fish and increasing the chance of secondary infections
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Alexander Dindial of the University of Stirling.
view moreCredit: University of Stirling
A University of Stirling study could pave the way for the more efficient study of the secretions that salmon lice use to avoid fish defences, potentially enabling the development of new strategies to protect salmon from infestations.
Research led by PhD researcher Alexander Dindial alongside Professor James Bron and Dr Sean Monaghan at the University’s world-renowned Institute of Aquaculture, in collaboration with Moredun Research Institute’s Kevin McLean, has resulted in the development of a new and precise way to collect and study secretory and excretory products (SEPs) from salmon lice. This includes substances released from the glands of the lice that make it easier for them to feed or evade their host’s immune system.
Salmon lice feed on the skin, mucus, and blood of fish, causing open wounds that can lead to infection – reducing the market value of farmed fish and increasing the chance of secondary infections.
Various treatments have been developed to tackle sea lice infestations in Atlantic salmon aquaculture – which costs the industry more than $1b a year – but some of these can be expensive, unreliable, environmentally damaging, and negatively impact animal welfare.
Previous methods for extracting SEPs from salmon lice involved pooling together large numbers of individuals, hiding the natural differences between individual lice, which can provide a vital insight for developing targeted treatments or vaccines.
The new method, as well as allowing study of individuals, also reduces the potential for louse faecal contamination. It allows collection of high-quality samples from a single louse per test, with substantial yields of secretory proteins per louse.
Mr Dindial explained: “Salmon lice cause hundreds of millions of pounds of damage annually to the global salmon aquaculture industry through mortality, lost production and the implementation of control measures. Understanding these secretions is an important step towards understanding louse biology and developing new, safe, and effective strategies for control.”
Research involved collecting secretions from individual salmon lice by placing a small drop of solution over their mouths and letting them release proteins into it. These proteins were then examined using a technique called liquid chromatography tandem mass spectrometry to analyse the exact protein composition of each of the samples. This technique uses state-of-the-art equipment to separate the components of a sample, breaking it into fragments and analysing them - revealing protein composition and helping to identify them.
The team found 148 total secretory proteins, 64 of which were detected in each of the tested conditions – some of which could represent potential targets for vaccine development.
The secretory protein profiles of individual lice showed a wide variation in protein number and diversity, a pattern consistent with other ectoparasites like ticks and mosquitoes.
Mr Dindial continued: “This work has the potential to expand our knowledge of salmon louse biology and to provide insight into louse proteins that could be exploited to help fish mount an immune response against infection.
“The novel methodology developed here has the potential to directly facilitate further research into salmon louse secretory biology. It allows for the reproducible, reliable, and efficient extraction of high concentrations of salmon louse secretions, all while minimising faecal contamination.
“As well as improving the study of these secretions, the protocol could be used to investigate how drug or therapeutic treatments might alter louse secretory activity, ultimately advancing efforts to control this parasite.”
The work builds on a first-of-its-kind study led by Mr Dindial, published last year, that uncovered major differences in the secretions that the parasite uses to feed and evade the immune system at different stages of its life cycle.
Investigation of a novel assay for the proteomic screening of the secretory and excretory products of individual salmon lice Lepeophtheirus salmonis was published in Veterinary Parasitology.
This work was funded by EastBio as part of the study lead’s PhD studentship, with a funding contribution from Moredun Research Institute.
Collaborative research was conducted with the project Towards lice-resistant salmon: functional genetics and genome editing to enhance disease resistance in aquaculture, funded by UK Biotechnology and Biological Sciences Research Council (BBSRC), Sustainable Aquaculture Innovation Centre and Benchmark Genetics Limited and involved partners from Roslin Institute at the University of Edinburgh, the Centre for Environment Fisheries and Aquaculture Science. the Atlantic Veterinary College at the University of Prince Edward Island, and Kames Fish Farming Ltd.
Journal
Veterinary Parasitology
Method of Research
Experimental study
Subject of Research
Animals
Article Title
Investigation of a novel assay for the proteomic screening of the secretory and excretory products of individual salmon lice Lepeophtheirus salmonis
