Heidelberg Scientist Receives Highly Endowed ERC Synergy Grant
Prestigious funding by European Research Council for pioneering biomedical project
Prof. Dr. Dominik Niopek, a scientist at the Institute of Pharmacy and Molecular Biotechnology (IPMB) of Heidelberg University, has been awarded an ERC Synergy Grant for a pioneering biomedical research project involving collaboration between teams in Heidelberg, the United Kingdom and the United States. The European Research Council (ERC) is granting this prestigious funding to develop a method based on artificial intelligence with which antigens can be identified from antibody sequences alone. The interdisciplinary consortium project is at the intersection of immunology, parasitology, protein design and machine learning, and is coordinated at the German Cancer Research Center (DKFZ) in Heidelberg. The ERC has allocated approximately ten million euros in funding for a period of six years, of which just under 2.2 million euros are intended for Prof. Niopek’s research at the IPMB.
The focus of the research in the ERC project “Toward a Trypanosome-Informed Machine-Learning Framework for Bidirectional Antigen-Antibody Prediction” (TrypanoFormer) is the interaction of antibodies and antigens. Antigens are structures – generally proteins or other biomolecules on the surface of pathogens – which the immune system recognizes as foreign and against which it forms antibodies. Antibodies are proteins that bind their antigen with high specificity, thereby making it visible to the immune system. Crucial for recognition is the order in which the antibody’s amino acids are aligned, called the antibody sequence. This is where the ERC TrypanoFormer project comes in: a new method aims to identify the antigen an antibody recognizes from its sequence alone – and, conversely, to design antibodies tailored to a known antigen.
“Today we can read millions of antibody sequences within days. However, in most cases we don’t know what these antibodies really recognize in the body. So we can read the antibody repertoire but not decode it,” Dominik Niopek explains. If that were possible, a blood sample, for example, could reveal what the immune system has previously engaged with or its current concern. That could open up completely new opportunities for precision diagnostics. Yet the antibody-antigen data available today is nowhere near sufficient, in either quantity or diversity, to train the sophisticated AI models needed to decode this immune memory, according to the Heidelberg researcher.
In order to close this gap, Prof. Niopek – together with Prof. Dr. Nina Papavasiliou (DKFZ), Prof. Dr. Bill Wickstead (University of Nottingham) and Prof. Dr. Monica Mugnier (Johns Hopkins University) − wants to use what are called trypanosomes as “living data factories” to analyze many different antibody-antigen pairs. The microscopically small parasites wear a thick coat of a single surface glycoprotein, which they constantly exchange for new variants in the course of an infection. That means that new antigens continuously present themselves to the immune system while the previously formed antibodies become ineffective. In this way, trypanosomes constantly avoid the immune system of their host. The scientists want to make targeted use of this ability. The great diversity of the pathogen’s antigens makes it possible to generate a large number of antibody responses and, as a result, collect the data so far lacking for the training of AI models.
“By observing how the parasite and the immune system interact, we can capture a vast number of distinct antibody-antigen pairs, including hundreds of closely related sequences,” Prof. Niopek says. In this context, his group at the Institute of Pharmacy and Molecular Biotechnology, with Prof. Papavasiliou’s team, will develop a new antigen display procedure in order to bring selected antigens to the surface of the parasites. In addition, the IPMB is developing the machine learning models to be trained with the data gained. The goal of the studies is to draw as full a picture as possible of antibody-antigen interaction and hence broaden the understanding of antibody biology. In the long term, the new approach is also intended to help generate tailored immune responses through molecular engineering – a core research focus of Heidelberg’s Cluster of Excellence SynthImmune, in which Prof. Niopek and Prof. Papavasiliou are involved.
Dominik Niopek studied molecular biotechnology at Heidelberg University, where he also obtained his doctorate. From 2016 he pursued research as a junior group leader at the IPMB and the BioQuant Center of Ruperto Carola, and also completed a research stay at Harvard Medical School (United States). In 2020 he took up a professorship at the Technical University of Darmstadt, before accepting an appointment in 2023 at the Faculty of Engineering Sciences of Heidelberg University. Prof. Niopek heads the department of Pharmaceutical Biology at the IPMB, of which he is the managing director. With his team he uses engineering principles in order to make molecular precision tools with different applications in basic biomedical research. Dominik Niopek has received several distinctions for his work, among them the Life Sciences Bridge Award from the Aventis Foundation and an ERC Starting Grant.
The ERC Synergy Grants fund collaborative projects that, due to their complexity, are carried out by two to four scientists and their groups. In this way, the program seeks to enable scientific breakthroughs that no single research group could achieve alone.
