Solar energy harnessed by plants and algae has great potential to be converted into biofuels for future generations.

Phospholipase A/acyltransferase 3 (PLAAT3) and PLAAT4 are enzymes involved in the synthesis of bioactive lipids. Despite sequential and structural similarities, the two enzymes differ in activity and specificity.

Particles are omnipresent in biopharmaceutical products. In protein-based therapeutics such particles are generally associated with impurities, either derived from the drug product itself (e.g. protein aggregates), or from extrinsic contaminations (e.g. cellulose fibers).

How did toxin genes evolve from harmless physiological genes?

Promotores: H.S. Overkleeft; G.A. van der Marel Co-Promotor: B.I. Florea

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

While there are numerous and extremely advanced methods to sequence the genome, only a few methods exist to sequence the proteome. The Vidi project of Grégory Schneider promises to shed light on the most difficult paradigm of proteomics: achieving an error-free determination of the sequence of single…

How do our cells keep DNA stored away? To find out, biochemist Remus Dame received a 3 million euro Science-Groot grant. Leiden University will share the grant with TU Delft, VU Amsterdam and the Hubrecht Institute.

At high doses, drug candidate BIA 10-2474 binds not only to the protein that it targets, but to other proteins as well. It thus deactivates proteins that are involved in the metabolism of nerve cells. This is what an international group of researchers from Leiden University and Erasmus MC, among others,…

Protein chains typically fold to function. Folding is a complex process and if done correctly leads to a unique functional fold topology for a given protein chain. Other topologies are also possible but are often non-functional or toxic. These misfolded proteins are then unfolded and subsequently refolded…

Alireza Mashaghi from the Leiden Academic Centre for Drug Research (LACDR) will use state-of-the-art technology to investigate proteins that play a role in muscular dystrophy. His goal is to provide new insights for designing novel therapeutic strategies in the future. To accomplish this, Mashaghi receives…

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

The chemical synthesis of inhibitors and probes targeting endo-glycosidases.

Promotor: J.N. Kok, P.E. Slagboom Co-promotor: J.F.J. Laros

Promotores: A.P. IJzerman, H.W.T. van Vlijmen

Promotores: H. Schiessel, G.T. Barkema

The team of Alireza Mashaghi at the Leiden Academic Centre for Drug Research has found a way to determine and classify the shape of proteins. Their new theory defines the topology of proteins as a simple and precise barcode that allows the identification of all types of folds. ‘This barcode enables…

Promotor: H.S. Overkleeft, Co-promotor: B.I. Florea

We aim to unravel the molecular mechanisms involved in the transformation of eukaryotic cells by Agrobacterium.

Poly(lactic-co-glycolic acid) (PLGA) particles have been extensively studied as biodegradable delivery system to improve the potency and safety of protein-based vaccines. In this study we analyzed how the size of PLGA particles, and hence their ability to be engulfed by dendritic cells (DC), affects…

Promotores: Prof.dr. C.A.M.J.J. van den Hondel, Prof.dr. V. Meyer (Technische Universität Berlin)

The type-IV secretion system (T4SS) is a machinery able to transfer DNA and proteins between bacteria and in certain cases also to eukaryotic cells.

The high prevalence of pure red cell aplasia in Thailand has been associated with the sharp increase in number of recombinant human erythropoietin (rhEPO) copy products, based on a classical generic regulatory pathway, which have entered the market.

Promotor: Prof.dr. A. P. IJzerman, Co-Promotor: Dr. L.H. Heitman

This thesis describes the use of an activity-based proteomics method to study the endocannabinoid system.

BlaC is the β-lactamase of Mycobacterium tuberculosis. We show that it can recover from inhibition by clavulanic acid and that phosphate helps it do so.

Autopaghy is an intracellular degradation system which targets cytosolic components to lytic compartments for degradation and recycling of the building blocks of the cell.

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.

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

Vitamin A or retinol is essential in embryonic development, the visual cycle and the immune system.

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

Less than 1 in 10 drug candidates that enter phase 1 clinical trials actually gets approved for human use.

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.

This thesis explores different avenues to develop insurmountable antagonists for CC Chemokine Receptors, such as CCR1, CCR2 and CCR5.

Source: Biosens Bioelectron, Volume 74, pp. 233-42 (2015)

In photoactivated chemotherapy (PACT), a biologically active compound is caged by a light-cleavable protecting group.

During the course of drug discovery translational steps are made.