As of 1 November, Laura Heitman has been appointed full Professor of Molecular Pharmacology at the Leiden Academic Centre for Drug Research (LACDR). Heitman has been working on the understanding and improvement of drug-receptor interactions in early drug discovery. ‘My ultimate aim is to make medicines…

Target selectivity is an important aspect of any drug molecule, and certainly a parameter to be optimized. That is not trivial for a number of reasons. First of all hundreds of drug targets (receptors, enzymes, ion channels) exist, and no single lab in the world has assays for all of them.

Researchers at Leiden University led by Mario van der Stelt (Leiden Institute for Chemistry) have set ‘gold standards’ for developing new painkillers based on the medicinal effects of cannabis. Publication in Nature Communications.

In this thesis, we have studied the potential of the zebrafish larval model in studying the ECS, as a complementary model to the existing rodent models.

Bacterial chemosensory arrays are protein assemblies that are the key structural and functional component for motile bacteria to sense their internal or environmental chemical signals.

Promotores: H.S. Overkleeft, G.A. van der Marel, Co-Promotor: J.D.C. Codee

PhD Defence

Promotores: Prof.dr. M. Danhof, Prof.dr. D.R. Stanski

Source: Structure , Volume 22, Issue 8, pp. 1120-1139 (2014)

This thesis focuses on the role of chemokine receptors CXCR3 and CCR2 in the inflammatory process and infection control using the zebrafish model.

Activity-based protein profiling (ABPP, also termed chemical proteomics), is one of the pillars of chemical biology, and at LED3 we have taken it to the next level. ABPP allows the assessment of protein function in live cells and tissues, which means that the activity of a complete protein family can…

Leiden has a long history in the treatment of blood cell cancer. Research to find better therapies never stands still. One of the potential treatments currently being worked on is a ‘living medicine’.

A tantalizing concept that has emerged in our recent research is binding kinetics. An important parameter is residence time (RT), a direct reflection of how long a drug stays bound to its target. This parameter is of crucial importance, because drug action lasts only as long as the receptor-ligand complex…

Designing and synthesizing high-affinity ligands for a given drug target have always been among the more important challenges in the drug discovery process.

In order to gain insight into the structure and function of the molecular complexes involved in chemotaxis, we use electron cryotomography (ECT). This technique allows us to directly study microbes in their native state at resolutions capable of visualizing individual proteins.

We have examined sequences from the ligand-binding domain of the nicotinic acetyl choline receptor (nAChR) in 148 vertebrate species. We are in interested in this receptor because the α-neurotoxins of many venomous snakes binds to this receptor in its location at the neuromuscular junction in all ve…

The Leiden Academic Centre for Drug Research (LACDR) received no less than three awards during the Figon Dutch Medicine Days. Bas Goulooze won the PhD Prize for best PhD candidate, Natalia Ortiz Zacarías and Huub Sijben both received a poster prize. ‘Scientists must be able to communicate their research…

Visualization of biomolecules in living cells by tagging with gold nanoparticles.

Macrophages and atherosclerotic lesions The infiltration of monocytes in the arterial wall, their differentiation to macrophages, and the subsequent accumulation of cholesterol in these macrophages initiate the process of atherosclerosis. We study the importance of specific genes in macrophages for…

Exploring the mechanism of targeted nanoparticle-mediated drug delivery using the zebrafish model

The CIGR comprises research groups from the Institute of Biology Leiden (IBL), the Leiden Institute of Chemistry (LIC), the Leiden Academic Centre for Drug Research (LACDR) and the Leiden Institue of Physics (LION).

PhD Defence

Gerrit van Dijk was born on 14th August 1939 in Kampen. He studied Mathematics in Utrecht where he also received his PhD in 1969 on the thesis ‘Spherical functions on the p-adic group PGL(2)’. His supervisor was prof. dr. T.A. Springer. The academic year 1969-1970 he spent in Princeton, at the Institute…

Promotor: Prof.dr. B. van de Water, Co-promotores: J.W. van der Laan, C.L.E. Siezen

Supervisor: Gerard van Westen

A study by a Leiden-Wageningen group shows that present-day humans are biologically poorly equipped to deal with the toxins they are regularly exposed to in smoky environments: compared to earlier hominins, we modern humans are probably even worse off. The study appeared in Molecular Biology and Evolution.…

In this thesis, we used genetically engineered mouse models to identify genes and pathways that are involved in ILC formation and in the development of resistance to FGFR-targeted therapy.

Monoacylglycerol lipase (MAGL) is the principal enzyme responsible for hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibition provides several potential therapeutic opportunities, including anti-nociceptive, anti-inflammatory and anti-cancer activity.

Due to the modern techniques of combinatorial chemistry and high-throughput screening, data on the biological activity of many millions of compounds is known. However, it is still very difficult to transfer this data into knowledge: if we know that compounds A and B bind to a certain protein with high…

Intrigued by the way cells autonomously regulate their fate, we strive to understand and visualize cellular processes as the basis of Cell Signaling.

The research of the Van Eck Group focusses on 3 interconnected research lines: 1) Identification and therapeutic targeting of key pathways/regulators in macrophages essential for prevention of atherosclerotic lesion development or stimulation of regression of existing lesions, 2) Atherosclerosis as…

For more information regarding ongoing research projects, please contact Prof. Miranda van Eck.

Cell adhesion signaling

Establishing human induced pluripotent stem cell (iPSC) CRISPR-Cas9-based fluorescent reporter cell lines for NF-kB signalling. We will use this to enable studying the dynamic activation and downstream signalling of Toll-like receptor and cytokine signalling in iPSC-derived differentiated cells in a…

Lecture

PhD Defence

The Data-Driven Drug Discovery Network (D4N) is an initiative by researchers from Leiden University and collaborators to join efforts in applying and developing novel techniques from data science to drug discovery and related topics from bioinformatics.

Laura Heitman has been awarded a VIDI grant for her innovative drug research. Heitman strives to optimize a drug’s binding kinetics at its target in order to ultimately fight diseases effectively. She even pleads for a paradigm shift in drug discovery.

There are many complex links in the chain that provides patients with new drugs: from fundamental science, to clinical tests, to production. The entire chain can be found in Leiden. Leiden University, the Leiden University Medical Center (LUMC) and the businesses at the Leiden Bio Science Park (LBSP)…

What are the biological and biophysical mechanisms that control chemokine gradient sensing and migration of immune, endothelial, and tumour cells in tumour development?

Selected publications of the Cardiovascular and Metabolic Therapeutics group.

Relevant publications of the CIGR participants.

In neonates and infants, body size, enzyme pathways, and expression and function of receptors and (target) proteins are still developing.

The disease acute myeloid leukemia (AML) is characterized by fast progression and low survival rates.

Supervisor: Anna Vlachodimou

Description of Biotic ligand models: making an inventory of available models & assessment of the variability of the predicted HC5 using the BLMs in different Dutch water types (2005 - 2007)

Bacteria caught red-handed, deeply frozen just as they were about to cause Lyme’s disease. Ariane Briegel is wildly enthusiastic about the wonders she observes thanks to three elements: a freezing technique, a camera-equipped microscope, and AI. ‘It’s fascinating. Every single cell is different.’

In the hunt for a vaccine against cervical cancer, fundamental knowledge about the immune system and organic chemistry have been brought together and have already resulted in a vaccine that is now being tested in clinical trials. Scientists are now working hard on an improved variant.