High-throughput holistic preclinical screens are increasingly used in drug discovery, to assess both drug efficacy and drug safety.

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.

Which plant leaf characteristics are involved in thrips resistance in tomato?

A next, general pharmacological problem to be tackled is how drug-target binding kinetics in vivo, affects target occupancy as an important indicator of the time-course of drug effects.

Harm reduction in practice: a comparative analysis of the Dutch and Brazilian approach towards drug users.

Promotor: Prof.dr. B. van de Water, Co-promotor: L.S. Price

Can thrips resistance in strawberry be explained based on secondary metabolite profiles and plant morphological traits?

Discovery of metastasis promoting candidate drug targets

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.

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…

Several single-stranded RNA viruses make use of Xrn1-resistant RNAs in their 3’ untranslated regions of their genome RNAs in order to increase their pathogenicity.

Why do communities form militias to defend themselves against violence during civil war? Using original interviews with former combatants and civilians and archival material from extensive fieldwork in Mozambique, Corinna Jentzsch (Leiden University Institute of Political Science) explains the timing,…

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Over several decades, a variety of computational methods for drug discovery have been proposed and applied in practice. With the accumulation of data and the development of machine learning methods, computational drug design methods have gradually shifted to a new paradigm, i.e. deep learning methods…

An interdisciplinary collection of the best international scholarship on Muslim youth.

Actinobacteria are well known for the production of bioactive natural products, many of which have applications in the fields of human, animal and plant health. Subject of this thesis are the anthracyclines, glycosylated aromatic polyketides with potent anticancer activity.

Actin and microtubules form cellular cytoskeletal network, which mediates cell shape, motility and proliferation and are key targets for cancer therapy. Changes in cytoskeletal organization correlate with proliferative capacity and invasiveness of cancer cells. These changes expectedly lead to altered…

Benjamin Fogarty-Valenzuela published the article 'Pedagogies of Prohibition: Time, Education, and the War on Drugs in Rio de Janeiro’s Zona Norte' in Cultural Anthropology 37. The article’s three sections focus on three forms of temporal control—busyness, punctuality, and rhythm—and each demonstrates…

The Minor Computational Approaches to Disease, Signaling and Drug Targets (CADSDT) is focused on fundamental scientific research required for discovery of new drug targets and development of new drugs.

Promotor: Prof.dr. M. Danhof, Co-Promotor: J. de Jongh

This thesis focuses on the application of lipid-based nanomedicine in drug delivery, including small molecular antitumor drugs and biomacromolecules including mRNA, and evaluates their biological performance.

Can we develop a generic method for Quan/Qual analysis of small molecule drugs, their metabolites and endogenous metabolites in (pre-)clinical samples?

Although rarely considered by the pharmaceutical industry or clinicians, 24-hour rhythms in physiology are a factor of potential influence on the pharmacokinetics and pharmacodynamics of drugs.

Another research line is the development of a spatial CNS drug distribution model, by ultimately including the 3-dimensional anatomical organization of the CNS.

How can we extend the drug residence time to combat diseases more effectively?

Streptomyces are multicellular, Gram-positive bacteria in the phylum of actinobacteria which produce a high amount of bioactive natural products of which the expression is tightly coordinated with the life cycle.

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

Source: ChemMedChem (2015)

Heart failure is a major health care problem with high mortality.

During the course of drug discovery translational steps are made.

Fungal food spoilage often starts with a contamination with spores. Experimental data strongly indicate the existence of subpopulations of spores with different levels of resistance to preservation methods.

Can a new proteomics workflow be developed to link genes and gene clusters to bioactive molecules, identify novel compounds and enhance the production in the Streptomyces lividans enzyme?

Data analysis with Python and R are rapidly becoming essential skills for modern scientists. Therefore, we are offering courses to develop your scientific computing skills. Those courses are optional for LACDR PhD candidates.

Human and animal cells are very complex: very different chemical processes are going on at the same time, but they are separated from each other because the cells are divided in compartments. These compartments may also have a profound effect on the potential efficacy of therapeutics, because the drug…

The GMP Facility facilitates development and production of Advanced Therapy Medicinal Products (ATMPs) and chemical (peptide) synthesis.

Promotor: A. Kros

No, this isn’t about a Star Wars Alliance that wants to suppress The Resistance. Rather, the EPIC Alliance brings together scientific experts from seven countries to address the growing threat of antibiotic resistance. Leiden professor Nathaniel Martin is part of the 11-member consortium.

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…

Biosynthetic gene clusters (BGCs) for natural products are widespread in microbial genomes, and they are rapidly exchanged. This research assesses the factors that control the spread of BGCs and resistance genes in nature. This includes risk assessment for the spread of engineered DNA in nature.

Though tuberculosis can be cured today, new resistant strains of the bacteria are becoming a growing problem in the medical world. Biologist Annemarie Meijer and her colleagues are studying resistance to this disease. Their research is already yielding several interesting clues that could help the development…

Rosan Kuin started her PhD in July at the LACDR under supervision of prof. Gerard van Westen and Dr. Meindert Lamers. She completed a BSc. in Pharmaceutical Sciences at the VU University in Amsterdam in 2017. After that she started two master programs, Drug Discovery & Safety with a specialization in…

The ethics of ghosts, spectres, and mediums in postcolonial literature

Employer organizations have been presented as strong promoters of the liberalization of industrial relations in Europe. This article, in contrast, argues that the preferences of employers vis-à-vis liberalization are heterogeneous and documents how employer organizations in Spain, Italy, and Portugal…

Promotores: Prof.dr. H. S. Overkleeft, Prof.dr. G. A. van der Marel

Clinical development of drugs for central nervous system (CNS) disorders has been particularly challenging and still suffers from high attrition rates.

Promotor: A.P. IJzerman Co-promotor: L.H. Heitman