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

PhD candidates carry out a programme of independent research and additional (limited) course work, culminating in production of a PhD thesis in typically 4 years.

This is an Erasmus+ International Credit Mobility project of the Faculty of Sciences with one partner in Ukraine.

Bicarbonate buffer is largely found in nature due to its ability to regulate pH variations around neutral values. As the pH changes, so does the speciation of the buffer.

Metal complexes and 2D materials like graphene were combined to produce structures that can function as sensors.

The first steps are made in personalised cancer vaccination strategies, which aim to induce a more specific immune response with fewer side effects. The activation of cytotoxic T cells is crucial for an effective immune response.

In this thesis, we study different curved single crystals because of the diversity of surface structures across their curvature.

Hydrodesulfurization (HDS) is an ubiquitous part of oil refining that ensures that fuels are cleaned of impurities and environment release of pollutants such as SOx and NOx gasses are minimized.

The relative simplicity of the bacterial cell, short generation times and well defined and inexpensive culturing conditions have significantly contributed to our understanding of many complex biological systems. Yet the workings of the bacterial genome, seemingly impossibly compressed within a tiny…

Zebrafish is an excellent model organism for studying various human diseases. Due to opaqueness of the adult phase, in vivo studies are restricted to early embryonic stages. This raises the need for rapid sensitive and non-invasive in vivo imaging methods to follow developmental processes, not only…

This work has described synthetic strategies towards well-defined structures resembling capsular polysaccharide (CPS) fragments, CPS mimics, teichoic acid (TA) fragments as well as a third-generation ring-closing tandem metathesis (RCM) linker to better exploit the potential of automated synthesis.

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

Promotor: Prof.dr. J.P. Abrahams, Prof.dr. M. van Heel

This thesis describes the use of a combined approach of computational and experimental techniques to gain novel insights to understand the glycosylation reaction and its reactive intermediates.

Carbohydrates, or sugars, are the most diverse and most abundant biomolecules known. However, the isolation of carbohydrate samples in sufficient amounts and purity is often impractical or even impossible, so the chemical synthesis of glycosides becomes relevant. The glycosylation reaction, in which…

Microscopic insight on lipid-based nanomedicine in vivo remains limited to the perception of the knowledge that could be obtained: if we interpret only what we see, then we only believe to know. Although believing to know encapsulates an undefined amount of uncertainty in the exploration of lipid-based…

Enzymes are innately sensitive to changes in the amino acid sequence, which largely constrains their evolutionary potential, i.e., evolvability. This evolutionary burden can be alleviated in the presence of stabilizing mutations, which increase the buffering capacity of enzymes to tolerate mutations…

Ice, the solid state of water, plays an important role on our planet as well as the entire universe.Despite the fact that an individual water molecule has a very simple structure, its chemical bonding in the solid phase can be surprisingly complex.

Kinase inhibitors are key therapeutic agents, particularly in oncology, yet their clinical efficacy is often hampered by off-target effects and limited understanding of their cellular target profiles.

As leading cause of death worldwide, cancer is responsible for nearly 10 million deaths in 2020 according to World Health Organization (WHO). Cisplatin and its derivatives are commonly used chemotherapy agents for current cancer treatment in the clinics.

Reducing greenhouse gas emissions is one of the most pressing challenges that humanity faces in the coming decades.

In the current global context, there is a pressing need to address sustainable energy supplies to safeguard our Planet and its ecosystems. The choices made by human society have a significant impact on genetic evolution and climate.

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.

In this work, we illustrate unconventional approaches towards the fabrication of edge functionalized graphene nanostructures and bidimensional architectures in polymeric and metallic supports, with an outlook towards molecular sensing devices.

The endocannabinoid receptors CB1R and CB2R are involved in a plethora of processes, and consequently are involved in many pathological conditions. Their wide distribution makes the CBRs both an interesting therapeutic target and hard to study.

The long-held desire - to link structure directly to function and to explain molecular mechanisms based on basic chemical or physical principles - is finally coming closer, satisfying not only our scientific curiosity but also offering new solutions to the many challenges in the field of health, energy…

Promotor: A. Kros, Co-promotor: R.R.C.L. Olsthoorn

Due to their central physiological roles in living organisms, retaining beta-glycosidases have been the subject of tremendous research efforts to examine their structure/function relation using numerous biophysical and biochemical approaches.

The growing demand of energy indicates that global energy resources in the form of fossil fuels will not be sufficient in the future. In order to solve potential future energy problems development of a sustainable hydrogen economy is highly desirable.

The research presented in this thesis makes use of small molecules (as H2 , D2 and O2 ) on well-defined single crystal surfaces (flat Pt(111), flat Cu(211) and curved Pt(111)) to elucidate the role of surface structure and degrees of freedom in the reactant in specific surface reactions.

Protein–protein complexes are formed via transient states called encounter complexes that greatly influence the formation of the stereospecific complex.

Glycosidases are important enzymes in the turnover of polysaccharides and glycoconjugates, and are involved in a range of human pathologies including genetic disorders such as Gaucher and Pompe disease, but also in various cancers.

Antibiotic resistance, caused by widespread use of antibiotics, leads to bacterial infections that are difficult, if not impossible, to treat and is a major worldwide health concern.

PNAS publication on protein encounter complexes

This thesis describes the use of bioorthogonal proteins in immunological settings. It provides an introduction towards the field of protein modification, which was used throughout the thesis for the expression of proteins containing unnatural amino acids.

Carbon dioxide capture and utilization technologies are necessary to create a truly circular economy. The electrochemical reduction of carbon dioxide to formate is an appealing carbon utilization method as it can be performed at room temperature and pressure, it only requires two electrons, and it has…

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.

Promoter: J.G.E.M.Fraaije, Co-promotor: A. Kros

Curved single crystals provide variable, but well-defined surface structures.

Promotor: G.A. van der Marel, Co-promotor: D.C. Codée

β-Lactamases are enzymes that can break down β-lactam substrates, such as antibiotics, preventing the use of these antibiotics for the treatment of various infectious diseases. However, some compounds, β-lactamase inhibitors, can block these enzymes allowing for possible treatments using a combination…

Promotor: E. Bouwman, Co-Promotor: S. Bonnet

Advanced UHF MRI techniques provide powerful tools for studying the zebrafish brain, an emerging model in neurological research. In this work, various MRI and localized MRS methods are optimized and employed for UHF strength for studying the zebrafish brain.

Promotor: A. Kros

This thesis describes the synthesis and biological evaluation of TLR2/6, TLR4, TLR7/8 and TLR9 ligands, of which the activity can be conditionally controlled.

Heterogeneous catalysis is one of the fundamental processes of modern life, being common in industrial refinery and hydrogen vehicles, all the way to the living cell. The dissociation of H2 on Cu(111) is an important benchmark system for studying heterogeneous catalysis, with a large and varied amount…

Solar energy is used by photosynthetic organisms to drive energy required cellular processes. Is absorbed by two groups of pigments, located in the LHCs.

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.

Marc Koper’s research focuses on electrocatalysis and electrochemical surface science for sustainable energy and chemistry. Reactions of interest are the redox reactions of the oxygen/hydrogen cycle (water oxidation, hydrogen evolution), the carbon cycle (reduction of carbon dioxide, oxidation of small…

All life on earth contains DNA, which is used to store biological information. Organisms compact their DNA in order for it to fit inside their cell(s).