FLOW consortium to acquire a complete understanding of the cell's quality control network.

In the 2024 round of NWO Gravitation grants, the new consortium FLOW was awarded 23 million euros. Running from 2024 to 2034, FLOW will investigate the cellular factors that determine the fate of proteins throughout their life and learn how to influence that fate.

A chemically modified version of the antibiotic vancomycin is much more effective against MRSA and other Gram-positive bacteria than the original. Leiden university professor Nathaniel Martin and his group developed this guanidine modified lipoglycopeptide. They recently published their findings in the journal Science Translational Medicine.

A promising target for cancer therapeutics is the protease family of cathepsins. Researchers from the Swiss EPFL institute in collaboration with Dutch researchers from Radboudumc in Nijmegen succeeded in developing a highly specific, targeted way of inhibiting cathepsin activity. The results were published in May 2024 in the journal Nature Chemical Biology.

Postdoctoral project: Innate immune activation and sterile inflammation in microglia in human brain

Timo Oosenbrug is fascinated by immune receptors. "It is the first line of defense against viruses," he explains. "But what makes it even more interesting is what happens when these receptors keep firing all the time, causing sterile inflammation. The translation to this clinical condition is exciting."

Remarkably, we don't know everything about the common cold virus HKU1, part of the coronavirus family. ICI researcher Joost Snijder (Utrecht University) and his team recently not only proved where and how HKU1 binds to the host cell, but also showed how this binding triggers a remarkable conformational change of the spike protein that is fundamental to how this virus enters the cell.

Early 2024, a remarkable publication appeared in Science in which Florian Winau at Harvard and his team describe how they discovered the function of a specific glycolipid called Gb3 found on B cells. From their results, they conclude that Gb3 has the potential to act as an adjuvant to improve vaccines against viral infections such as influenza.

PhD project: Targeting metabolism of the enteric glial cell in Parkinson’s disease

The enteric nervous system possibly plays a key role in Parkinson’s disease, making it a target for possible treatment. Anastasia Markidi at Utrecht University set studies the effects of bacterial metabolites on enteric glial cells.

PhD project: The role and effect of pathogenic amyloid proteins on neutrophil extracellular trap formation in the central nervous system

Enebie Ramos Cáceres is a jack of all trades: his PhD project comprises chemistry and immunology and he is doing all that on his own. He not only develops chemical probes to study key enzymes related to NETosis, relevant to Alzheimer's disease, but he also collects, prepares and studies human blood samples to test his probes.

Omics data sets are an increasingly important part of the research of wet-lab cell biologists and immunologists. But they are usually not equipped with enough bioinformatics or coding skills to be able to analyse these data sets. A first for PhD students in the ICI program, this spring they had the opportunity to participate in the online training "Omic data analysis and visualisation using R" which focuses precisely on these skills.

Targeted anti-cancer therapies are the future of cancer treatment. Immunotherapy is booming, and antibody-drug conjugates (ADC) are a fast growing class of therapeutics. These consist of a cytotoxic drug connected to an antibody that targets a tumor marker. Although much research is aimed at elements of ADCs such as the drug payload or constructing nanobodies, the international research program TACT is bringing all aspects of this research together, from fundamental chemistry to the initial stages of biological assessment. ICI-partner WUR is involved.
The EU-project TACT combines state-of-the-art research in antibody-drug conjugates with extensive training of new researchers. (Image: TACT)

Herpes viruses can invade the nervous system and stay there unnoticed for a long time, before causing disease. But not much is known about the interactions between the virus and the nerve cells. Sabrina Krepel finds out using advanced techniques such as mass spectrometry and electron microscopy.

Microglia play a crucial role in neuronal diseases such as MS or Alzheimer's. But there is a large gap in knowledge about the processes involving microglia and the development of these and other neurological disorders. Without understanding of the fundamentals, there is no chance of a cure. PhD student Viktor al-Naqib at NIN studies these fundamentals in cooperation with chemical immunologists in Leiden.

Thermal peptide exchange technology. The term sounds like a simple lab protocol. But at a closer look it's a perfect example of multidisciplinary, multi-group research where a fundamental background, a good idea and an interest in technology lead to new insights and relevant medical applications. What started as an idea from the labs of Sjaak Neefjes and Huib Ovaa has now grown into a user-friendly method for screening immune cell responses to any antigen, developed in a collaboration between multiple research groups. (Image: Jolien Luimstra)

UbiQ was founded in 2010 as a spin-off of the Ovaa-lab at the Netherlands Cancer Institute. The small company develops reagents for ubiquitin research and is involved occasionally in drug discovery projects, says co-founder Farid El Oualid. "Our mission is ultimately to help patients. With UbiQ, we aim to explore all possible drug targets using our technology, and to facilitate others to do their research by providing reagents."

It's an unconventional ICI-project in many ways. LUMC researcher Aysegul Sapmaz wrote the proposal to study ubiquitylation of Rab-proteins back in 2019 together with Huib Ovaa and Sjaak Neefjes. She then moved on to do the research herself in close collaboration with PhD student, Esther ter Linden from the Neefjes group.

A superfamily of four-transmembrane proteins called tetraspanins are organizers of the membranes of immune cells. Although ubiquitous, understanding the precise role of some of these tetraspanins in the complement system is the challenge in this combined project in Utrecht and Leiden.

An imbalance between two types of T cells causes problems in autoimmune diseases and cancer. A selective intervention in the activity of these cells could be a therapeutic strategy, but the question is: how? Researchers in Utrecht and Leiden are finding unique metabolic features that discriminate between the two types.