A different approach to the search for target sites for novel drugs: Anna Hirsch receives ERC Starting Grant

HIPS scientist Anna Hirsch receives an ERC Starting Grant of €1.5 million in order to establish innovative methods for the identification of drug target structures

Medicinal chemist Prof Anna Hirsch has been awarded an ERC Starting Grant of the European Union. The European Research Council (ERC) uses these funds each year to support scientists from around Europe. Working at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), a branch of the Helmholtz Centre for Infection Research (HZI), Hirsch and her team are investigating lead structures for the development of new anti-infective and antibiotic agents. The grant of €1.5 million for her project titled "Identification and optimisation of novel anti-infective agents using multiple hit-identification strategies" will be spread over five years. The research work for the project started in February 2018 and might accelerate the development of new drugs.

PM_ERC_Grant_Hirsch_590x240.jpgPremium European funding awarded to Prof Anna Hirsch. © HZI/HIPSMany bacterial infections have become difficult to control, because the respective pathogens have become resistant to antibiotics. Once these important drugs are no longer effective, life-threatening complications might occur. It is therefore an important goal of modern drug research to develop new antibiotics to which the bacteria are not resistant yet. The sequencing of entire genomes and subsequent analysis of their biological information has become an established modern approach to drug research. The starting point in the development of a new drug is the identification of a target protein – a so-called "drug target" – that has a key function in a disease. Researchers then attempt to identify substances that have an effect on the target protein such that the corresponding disease can be mitigated or cured. A classical example is the specific inhibition of an enzyme by a chemical compound.

This is the essential field of research of medicinal chemist Anna Hirsch. It is one of her focuses to develop new lead structures for small molecules that make an infection by a pathogen more difficult or even impossible. The structure-based design of the molecules for new medications is always key to her work. Her approach has already been successful in the case of promising inhibitors that are being used as a starting point for the development of new anti-infective agents, in particular anti-malaria agents and antibiotics.

Developing new effective methods for the discovery of new lead structures is getting increasingly important. Hirsch's research will be funded for the next five years by an ERC Starting Grant worth €1.5 million. "We will concentrate specifically on target sites of proteins of multi-resistant bacteria that have not been characterised in much detail yet - so-called under-explored targets," Anna Hirsch says. She and her team of 18 scientists will use existing and innovative techniques in uncommon ways. They aim to discover new classes of structures for the development of new antibiotics against Gram-negative bacteria such as the hospital pathogen, Pseudomonas aeruginosa, or Gram-positive bacteria such as Mycobacterium tuberculosis and Staphylococcus aureus.

One of these innovative methods is called dynamic-combinatorial chemistry. "This technique is new in that the drugs are not synthesised fully, but merely as individual building blocks which react with each other in situ, i.e. in the test tube, Hirsch says. This allows the drug target to select the best inhibitor. She sees much potential in this new approach that might allow the process of drug development to be accelerated. In addition, it is expected to be applied in a wide range of medicinal-chemical projects in the future.

ERC Starting Grant:
The ERC Starting Grants provide funding to promising scientists at the start of their independent careers, who aim to set up their own research group. For more information, please visit: https://erc.europa.eu/funding/starting-grants

About the awardee:
Anna Hirsch majored in Natural Sciences at the University of Cambridge (England) with a focus on Chemistry. She did her doctoral work on "A Novel Approach towards Antimalarials: Design and Synthesis of Inhibitors of the Kinase IspE" under the supervision of François Diederich at the ETH Zurich (Switzerland). After her postdoctoral work in Strasbourg (France) under the supervision of Jean-Marie Lehn, Anna Hirsch became Assistant Professor (in 2010) and then Associate Professor of Structure-Based Drug Development at the University of Groningen (Netherlands, in 2015). She has been the head of the "Drug Design and Optimisation" department at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) since 2017. Hirsch aims to promote Medicinal Chemistry at Saarland University and at HIPS, aiming to further increase their international recognition in her field: the development of new anti-infective agents and hit identification methods. Anna Hirsch has received the following awards: Gratama Science Award (2014), SCT-Servier Prize for Medicinal Chemistry (2016) and the GdCh/DPhG Innovation Award for Medicinal Chemistry (2017).

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