The plant hormone auxin plays a central role in the growth and development of plants. Auxin acts in a concentration dependent manner and polar cell-to-cell transport of this hormone determines its distribution in the tissues of plants. This polar auxin transport is mediated by several families of auxin…

Promotor: H.S. Overkleeft, J. Neefjes, Co-promotor: M. van der Stelt

Promotor: Prof.dr. H.P. Spaink Co-promotor: Dr. B.E. Snaar

Promotor: Prof.dr. P. Hooykaas, Co-promotor: Dr. R. Offringa

The PID-directed shift in PIN polarity has been broadly accepted as one of the essential mechanisms for the regulation of auxin transport polarity.

Plants, are sessile organisms, have developed strategies to adapt to changes in their environment, in part by altering their growth and development.

Can we determine the 3D structure of a chemotaxis core complex using single-particle reconstructions via cryo-EM?

Chemical tools to monitor drug-target engagement of endogenously expressed protein kinases are highly desirable for preclinical target validation in drug discovery. Here, we describe a chemical genetics strategy to selectively study target engagement of endogenous kinases.

Triple-negative breast cancer (TNBC) constitutes a small subtype (~15%) of breast cancer, but causes the majority of breast cancer-related deaths.

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

Promotores: Prof.dr. M.K. Richardson, Prof.dr. H.P. Spaink

Chemical biology research at the Leiden Institute of Chemistry is aimed at understanding biological processes at the molecular level to strengthen the knowledge base of human health and disease. The approach to achieve this goal is a fundamental chemical one; with the aid of chemical probes biological…

Drug development is a time- and resource-consuming process that starts with the discovery and validation of a (protein) target that contributes to pathogenesis or disease progression.

1. What is the exact role of PIN proteins in PAT? 2. How is PIN polarity established, and how is it modulated by AGC kinase-mediated phosphorylation? 3. What is the role of the AGC kinase, as modulators of PAT, in translating environmental signals, such as gravity, light or mechanical stress, to plant…

Plant researchers have been wrong for years about how plant growth and development are regulated, as Yao Xiao pointed out during his PhD project. They overlooked the role of a protein that turns out to be essential, just as it is in the development of animals and yeasts. In plants, it regulates the…

Key publications of the Computational Drug Discovery group

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.

Key publications of the Cancer Drug Target Discovery group

PhD Defence

The current projects of the Molecular Physiology group focus on proteins of the endocannabinoid system, kinases and antibacterial targets. MSc- and BSc-students can contact Jessica van Krimpen-Kraaijenoord to apply for research internships.

Cancer is the leading cause of death in the Netherlands, and, with over 100 different types of cancer, it’s not a simple disease. Today, skin, breast, lung, prostate and colon cancer are the most diagnosed forms. Therefore, the discovery and development of new drugs has the ability to significantly…

In CCLS several subgroups have formed, below you can find an overview of these groups with the names of the leading researchers and a short outline of the project.

This thesis describes the importance of being able to control the selectivity of potential drug candidates.

Leiden chemists have developed a new technique with which they can determine the role of kinases – a group of proteins – in a living cell. This technique makes it easier to find new drug targets for diseases such as cancer and rheumatoid arthritis. The team published the findings in the journal Nature…

Promotor: Prof.dr. J. den Hertog

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer.

Exploiting metabolic vulnerabilities to identify anticancer compounds in zebrafish synthetic lethality screens.

PhD Defence

PhD Defence

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.

Bachelor and Master students of all chemistry related studies are more than welcome to take part in our research activities. We have projects on design and synthesis of biologically relevant compounds within an ongoing research project. Supervision, following the apprentice/teacher model, is one of…

In the research programme Drug Discovery & Safety, we are interested in the efficacy and safety of new drugs and novel means to decipher these aspects. Hence, we employ advanced imaging and high-throughput screening techniques next to computational approaches such as chem- and bioinformatics.

The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.

In the last decades, activity-based protein profiling (ABPP) has emerged as a powerful chemical tool that may aid the ever-challenging drug discovery process.

In the search for new medicines against diseases such as cancer, a Leiden team has developed a new workflow. This approach combines artificial intelligence (AI) with molecular modelling and is suitable for finding unknown and innovative drug structures, the researchers proved.

An overview of the research at the Cancer Dug Target Discovery group.

Can drugs that target host signaling pathways be used to eradicate antibiotic-resistant bacteria?

The research conducted at the Leiden Academic Centre for Drug Research is clustered within the divisions of BioTherapeutics, Drug Discovery & Safety and Systems Biomedicine and Pharmacology.

Source: Mol Psychiatry (2015)

Key publications of the Systems Pharmacology group

Molecular Physiology is a research group at the Leiden Institute of Chemistry dedicated to the design, synthesis and application of chemical tools to study important biological and biomedical questions. The group is headed by Prof. Dr. Mario van der Stelt and includes the research lines of Assistant…

Researchers at Leiden University have mapped genes that cause breast cancer cells to migrate. The Leiden toxicologists Professor Bob van de Water, Dr Wies van Roosmalen, Dr Sylvia E. Le Dévédec and colleagues studied 1500 individual genes. They found eight, including the SRPK1 gene, that regulate the…

We are interested in the efficacy and safety of new drugs and novel means to decipher these aspects. Hence, we employ advanced imaging and high-throughput screening techniques next to computational approaches such as chem- and bioinformatics.

Key publications of the Quantitative Pharmacology group

Leiden and Austrian researchers have succeeded in further uncovering how a plant cell passes on the growth hormone auxin in a directional manner to the next cell. Three proteins that cling together in a bunch appear to be essential for this important transport process. ‘This discovery solves a crucial…

During the congress of the Royal Dutch Association for the Advancement of Pharmacy (Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie, KNMP) Jacqueline Gerritsen, former student Bio-Pharmaceutical Sciences at Leiden University, was awarded the KNMP student prize.

The Chemical Probe Facility is part of the Leiden Early Drug Discovery & Development (LED3) center. Activity-based protein profiling (ABPP) is one of the pillars of chemical biology. ABPP determines the activity of entire protein families in living cells and tissues under physiological conditions, such…

Research in this group, headed by Gerard van Westen, focusses on computational methods integrated in different parts of the drug discovery process. More specifically, topics include innovative treatments for cancer, selectivity modeling, translational research, allosteric modulation, drug resistance…