Mechanisms fro drug resistance

Can effective synergists be identified to enhance the effect of antibiotics against Gram negative pathogens?

Optimised antibiotic combinations can combat bacteria more effectively while also slowing the development of resistance. Scientists from five European countries are joining forces to identify such combinations and provide tools for others to do the same. The project is led by Professor Coen van Hasselt…

The Leiden Academic Centre for Drug Research (LACDR) is a centre of excellence for multidisciplinary research on drug discovery and development.

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

Drug development is a complex process in which many parties work together. Every day, the researchers at LACDR devote their energies to developing drugs that are new, better, more efficient and easier to produce. And thus to the millions of patients who know all too well why this research in Leiden…

With the rise of multi-drug resistant bacterial pathogens, the possibility of a post-antibiotic world is quickly becoming reality.

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

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.

Drug-related homicide (DRH) has the potential to act as a valuable indicator of wider drug-related crime. Yet DRH remains a knowledge gap within this broader field of study.

The clinical potential of applying synthetic lethality to cancer treatment is famously demonstrated by the BRCA1/PARP1 paradigm: a tumor specific defect in BRCA1 – a component of the DNA double-strand break (DSB) repair pathway homologous recombination (HR) – results in a remarkable sensitivity to PARP1…

Knowledge of mental distress and resilience factors over the time span from before to after a stressor is important to be able to leverage the most promising resilience factors and promote mental health at the right time. To shed light on this topic, we designed the RESIST Study, in which we assessed…

The research within the Division of Cell Systems and Drug Safety, headed by Prof. Bob van de Water, is focused on novel therapeutic modalities and novel concepts in early drug discovery, in order to develop more effective and safer therapeutic strategies. We generate advanced cell and computational…

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…

Our research in the area of safety sciences aims to increase the mechanistic understanding of cellular toxicity of drugs and, in a broader sense, chemicals.

In this research group, headed by Bob Van de Water, cell signaling programs that underlie adverse drug reactions as well as cancer development and progression are unraveled. Adverse drug reactions involve cell injury in critical target organ cells which leads to the activation of cellular stress response…

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.

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…

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)…

Can metabolomic profiling be used to predict resistance against insect herbivores in plants?

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.

Promotors: C.A.J. Knibbe, Anthonius de Boer, Co-promotor: M.M.J. van der Vorst

In the Drug Research theme, we primarily work with rodents. Rodents, such as mice, are one of the most common laboratory animals. These small mammals are easily housed and exhibit a rapid rate of reproduction.

One of the stained glass windows in the Great Auditorium of the Academy Building is dedicated to the students and staff of Leiden University who resisted, protested against, or became victims of the German occupiers. It depicts female figures alongside male ones.

Is is possible to better predict the validity of drug candidates?

This project will construct an inventory of possible conceptions of the resistance of the world to scientists’ claims and theories.

Inactivating mutations in BRCA1 or BRCA2 genes predispose to several types of cancer.

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…

Breeding for resistance becomes more and more important because we want to reduce the use of pesticides. A fast and cheap alternative can be to make use of morphological or chemical markers.

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…

Citizens in multiple crime-ridden countries strongly support the militarization of security—that is, placing the military in charge of traditional policing duties. Yet, we know little about the determinants of such support. Do people approve of militarization even in the face of human fatalities? Political…

Drug-target binding kinetics determine the time course of the central event in pharmacotherapy: Drug-target interaction.

In previous studies at our laboratory it was demonstrated that drug exposure of HepG2 cells can lead to an altered TNFα-induced NF-κB oscillatory phenotype, concurrent with a synergistically increased sensitivity for TNFα-induced apoptosis.

Promotor: M. Danhof Co-promotor: O.E. Della Pasqua

Improving healthcare with our scientific discoveries: that is the goal of pharmaceutical research at Leiden University. And there’s a lot involved in that. Our research starts with the discovery of the effect achieved by a particular substance, and sometimes continues all the way through to the development…

This project aims to assess the risk of spread of antimicrobial resistance genes in the environment derived from currently used synthetic biology approaches in the field of drug discovery.

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.

Polymyxins are clinically used antibiotics, discovered in mid-20th century. Once abandoned due to excessive nephrotoxicity, they are now used increasingly to address infections caused by multi-drug resistant Gram-negative bacteria.In this thesis, we describe the development and synthesis of analogues…

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’),…

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…

This thesis describes the structural and biochemical characterization of the β-lactamase BlaC from Mycobacterium tuberculosis (Mtb), and the Alr and YlmE proteins from Streptomyces coelicolor A3(2).Mtb is the main cause of tuberculosis.

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

Lecture

A novel mathematical model describes spatial-temporal drug distribution within one or more brain units, which are cubic representations of a piece of brain tissue with brain capillaries at the edges.

Supervisor: Indira Nederpelt

In the literature, several types of microneedles have been extensively described. However, porous microneedle arrays only received minimal attention. Hence, only little is known about drug delivery via these microneedles. However, porous microneedle arrays may have potential for future microneedle-based…

What makes some international organisations more likely to succumb to crises where others manage to survive or even thrive? And what can international organisations do to become resilient and withstand existential challenges? Political Scientist Gisela Hirschmann (Leiden University) studied the example…