Discovery of metastasis promoting candidate drug targets

In this thesis an activity-based probe was discovered that could visualize the activity of PLAATs. With an optimized gel-based ABPP assay in hand, screening of a compound library led to the discovery of alpha-ketoamides as a hit for PLAAT3.

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.

Diacylglycerol lipases (DAGLα and DAGLβ) are responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain and peripheral tissues. Selective DAGLβ inhibitors have been proposed as a potential treatment for inflammatory diseases with reduced potential for central…

The spindle-assembly checkpoint (SAC) is a safety mechanism which secures accurate chromosome segregation during mitosis.

Global healthcare is on the verge of an antibiotic availability crisis as bacteria have evolved resistance to nearly all known antibacterials. Identifying new antibiotics that operate via novel modes-of-action is therefore of high priority.

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

Promotor: G.P. van Wezel, Co-promotor: Y.H. Choi

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

N-acylethanolamines (NAEs), which include the endocannabinoid anandamide, represent an important family of signaling lipids in the brain. The lack of chemical probes that modulate NAE biosynthesis in living systems hamper the understanding of the biological role of these lipids.

The Discovery of El Greco: The Nationalization of Culture Versus the Rise of Modern Art (1860-1915)

From the Big Bang to superconductivity. Many ground-breaking discoveries have been made in Leiden University’s long history.

The goal of hit discovery is to identify suitable chemical starting points to modulate a drug target. A hit can be, a.o., a small molecule, a protein or mRNA. Hit identification is performed via rational design, genome mining, (targeted) library screening, or in silico approaches.

We focus on a better understanding of the mechanisms of cancer drug resistance and metastasis.

Despite recent advances in medicine, many devastating disorders like cancer and cardiovascular, neurodegenerative and infectious diseases still lack effective treatments. In order to address this challenge, we, as scientists from Leiden University, joined hands in the LED3 network. LED3, for Leiden…

In this research group, headed by Prof. Erik Danen, the aim is to unravel cellular signaling mechanisms in normal and diseased cells, with a long-standing interest in cell adhesion signaling. In complex multicellular organisms such as ourselves, a division of labor emerges where different tissues and…

The master's specialisation Drug Discovery and Safety at Leiden University provides students with research-oriented education into the discovery of new drug targets and new lead molecules, particularly in the field of cancer, through a combination of advanced imaging techniques (‘systems microscopy’),…

To get a feeling of how we operate at LED3 when it comes to Early Drug Discovery, please browse through our case studies. When you select a case study you’ll find relevant contacts.

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.

The goal of target discovery is to identify and validate proteins and biological pathways that are involved in the disease process. Modulating these target proteins and pathways with small molecules, therapeutic proteins or other biomolecules (e.g. mRNA) could deliver an effective and safe drug or v…

The investigations described in this thesis lay out strategies aimed at advancing antibiotic research and development. The examples presented revolve around two main approaches: understanding drug-target interactions and target identification.

From nanoparticles to colliding ice planets and from biological origami to new x-ray scanner techniques: this year again, our scientists have made wonderful discoveries. From the largest numbers to the smallest molecules and from the oldest galaxies up to the latest algorithms, take a look at each institute's…

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.

The drug discovery pipeline is used to describe the stages in drug discovery. The earliest stage concerns with the identification of potential targets and molecules ('hits') that can modulate their function, while more advanced stages are about developing these hits into viable experimental drugs and…

The Night of Discoveries is an annual event in Leiden, focusing on science and culture. The Young Academy Leiden is a recurring contributor to the Night of Discoveries.

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…

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.

How are new drugs developed? This question is central to the Minor Modern Drug Discovery (MDD), which covers the entire trajectory from disease to drug molecule and vice versa. The various research groups involved offer a complementary and interdisciplinary perspective by connecting the diverse subjects…

We cover the entire spectrum from target identification to the evaluation of the efficacy and safety of novel medicines in clinical practice.

'A spectacular new Philippine monitor lizard reveals a hidden biogeographic boundary and a novel flagship species for conservation' . CML-researcher Merlijn van Weerd has participated in a new article in Biology Letters about this discovery.

In Germany, the United States and even in Vietnam: all over the world, the Leiden discovery of the birth of two planets was shared. Astronomer Sebastiaan Haffert and his team were able to record multiple planets in the making for the first time and published their findings in Nature Astronomy. A unique…

Do understudied animals contain hidden species?

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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…

On 28 October 2022, Yao Yuan spoke at the conference in Rome on 'Understanding national security concerns in light of FDI screening', jointly organised by Università Telematica internazionale UNINETTUNO and Uppsala University.

Supervisor: Indira Nederpelt

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Lecture

For the first time, scientists have traced back a high-energy neutrino to its source in space. It was produced by a so-called blazar—a supermassive black hole. Researchers from neutrino detector IceCube report this in Science. ‘This is a milestone for neutrino science,’ says physicist Dorothea Samtleben…

It was her original Salterio from 1725, built by Michele Barbi, which Franziska Fleischanderl could coincidentally acquire in 2014 that ignited her passion for this special string instrument. Before, she was focussed on contemporary music with modern Hackbrett.