Agrobacterium tumefaciens, a gram-negative plant pathogen belonging to the family Rhizobiaceae, is the causative agent of crown gall disease, which can affect many plant species including agronomically important ones.

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.

Pseudomonas Aeruginosa is a Gram-negative bacterium which can form biofilms, increasing its resistance against antibiotics and the host immune system. Polysaccharides are an integral part of this biofilm, one of these polysaccharides is called Psl. PslG is a glycosidase, able to cleave this polysaccharide,…

Death in all types of melanomas is generally caused by metastasis. Uveal melanoma (UM) is the most common intraocular melanoma, there are currently no (patient-derived) animal models that faithfully recapitulate metastatic dissemination of UM.

This thesis describes biochemical investigations of glucocerebrosidase (GBA), the lysosomal β- glucosidase that is deficient in Gaucher disease (GD).

Synthesis and application of chemical biology tools to study immunomodulatory signaling lipids.

The filamentous bacteria Streptomyces are widespread inhabitants of terrestrial soils.

Streptomyces are prolific producers of enzymes and secondary metabolites, including more than 50% of all clinical antibiotics. This makes them highly attractive for medical, biotechnological, and industrial purposes.

Streptomyces present a valuable platform for natural product discovery. Lugdunomycin is a novel angucycline-derived polyketide from Streptomyces sp QL37, with unprecedented skeleton and antimicrobial activity.

Promotores: Prof.dr. H. van Veen & Prof.dr. W. de Boer (Wageningen University)

Lysosomal acid glucosylceramidase (GBA1) is a lysosomal enzyme that degrades glucolipids with its main substrate being glucosylceramide (GlcCer). Defects in the GBA1 gene lead to glycosphingolipidosis Gaucher disease (GD), in which the hydrolysis of GlcCer is impaired and therefore, it accumulates in…

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

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.

Glycosidases (GHs) are enzymes responsible for the degradation of carbohydrates and play many roles in human health and pathophysiology. Often, abnormal levels of glycosidase activity are markedly linked to human pathologies.

N-acylethanolamines (NAEs), including N-arachidonoylethanolamine (anandamide, AEA), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA), are signaling lipids that play an important role in different physiological process.

Neurodegenerative diseases pose a large medical and societal challenge. The etiology of these diseases is still poorly understood, which makes drug discovery for these diseases difficult.

Nanodiscs are small, disc-shaped structures designed to mimic biological cell membranes, composed of a lipid bilayer stabilized by scaffold proteins. Membrane proteins play crucial roles in essential processes such as nutrient and waste transport, molecular recognition, and cell signalling, making them…

Glycosidases are essential in fundamental biological processes and are responsible for the degradation of most (oligo)saccharides, glycolipids and glycoproteins.

Phosphorylation affects all four major biomolecules – proteins, lipids, carbohydrates and nucleic acids – and plays a pivotal role in the most fundamental cellular functions.

According to the amyloid cascade hypothesis, accumulation of beta-amyloid (Aβ) peptides initiates the pathological cascade in Alzheimer's disease (AD).

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.

The electrochemical oxygen reduction reaction (ORR) is an essential half-reaction for the utilization of hydrogen as a sustainable fuel, via the conversion of hydrogen to electrons and protons facilitated by the ORR. In the most common fuel cells, the ORR is requires high loadings of non-abundant platinum…

The lysosomal β-glucosidase named glucocerebrosidase (GCase) is a retaining β-glucosidase that hydrolyzes the glycosphingolipid glucosylceramide (GlcCer) to ceramide and glucose at acid pH.

Growth and development affect the metabolism of drugs administered to neonates, infants, and children.

To this day, all cyclophellitol-based inhibitors and ABPs have been close analogues of their natural substrate counterparts. As a result, these probes showed high selectivity towards their target glycosidases.

Atherosclerosis is the most important underlying process that drives cardiovascular disease, and is characterized by an accumulation of cholesterol which triggers an inflammatory response in the vessel wall.

In this thesis, a system pharmacology approach, integrating metabolomics, pharmacology and chemical biology, was applied to understand and modulate the endocannabinoid system across different model systems (cells, zebrafish, mice and humans).

Het onderzoek binnen de Faculteit der Wiskunde en Natuurwetenschappen omvat de disciplines wiskunde, informatica, sterrenkunde, natuurkunde, scheikunde, bio-farmaceutische wetenschappen, biologie en milieuwetenschappen.

Microglia support the central and peripheral nervous system by forming the first line of defense against hazardous events. Microglia are increasingly acknowledged as critical players in neurodegenerative diseases, highlighting them as potential therapeutic targets.

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This thesis describes the synthesis and biochemical evaluation of a variety of cyclophellitol based activity-based probes and inhibitors targeting various endo- and exo-acting retaining glycosidases. In the last two decades a variety of probes and inhibitors for (hemi)cellulose degrading enzymes have…

Promotie

Dr. Arthur Ram is met ingang van 1 september 2016 benoemd tot Opleidsingsdirecteur van de bacheloropleiding Biologie. Hij volgt daarmee Johan Memelink op.

Negentien Leidse recent gepromoveerde onderzoekers kregen deze herfst een Veni-subsidie van NWO toegekend, zeven daarvan zijn voor onze faculteit. Elke onderzoeker krijgt 250.000 euro voor drie jaar onderzoek. Landelijk werden161 projecten gehonoreerd.

Leids microbioloog Arthur Ram gaat in samenwerking met Peter Westgeest van Generation of Change VOF piepschuimvervanger produceren uit hernieuwbaar restafval. Hiervoor heeft de Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) een KIEM premie beschikbaar gesteld.

Dr. Peter J. Punt, werkzaam bij TNO, is benoemd tot bijzonder hoogleraar Industriële Biotechnologie en gaat zich richten op de moleculaire genetica van filamenteuze schimmels.

Op 20 november vond de lezing van Prof.dr. Han de Winde met voorbroodje plaats. Naast de vaste schare NGL leden waren veel jonge alumni van de Faculteit der Wiskunde en Natuurwetenschappen tot het onderwerp aangetrokken. Ze wilden graag een academische lezing bijwonen omdat ze niet allemaal in de wetenschap…

BRAIN Biotech en het Instituut Biologie Leiden (IBL) van Leiden Universiteit gaan samen een Aspergillus schimmelstam verder ontwikkelen. Deze zal in staat zijn meer te produceren en daarmee een biologische circulaire economie stimuleren. De samenwerking is gebaseerd op BRAINs moleculaire hulpmiddel…

Hermen Overkleeft ontving samen met Bobby Florea een Zenith subsidie ​​van het Horizon-programma van het Nederland Genomics Initiative voor hun voorstel Quantative functional enzyme profiling: a versatile strategy to monitor disease progression and to validate new therapeutic strategies'.

De keten die patiënten voorziet van nieuwe medicijnen, bestaat uit diverse complexe schakels: van fundamentele wetenschap, tot klinische tests, tot productie. Deze hele keten is aanwezig in Leiden. De Universiteit Leiden, het Leids Universitair Medisch Centrum (LUMC) en de bedrijven op het Leiden Bio…

Baanbrekend werk van een Europees consortium maakt het mogelijk om eenvoudig nieuwe enzymen te ontdekken en te bestuderen. Het consortium publiceert de nieuwe technologie in het gezaghebbende open access tijdschrift ACS Central Science.