A structural investigation of coiled coil peptides used as membrane fusogens, mimicing naturally occuring coiled-coil fusion proteins. Synthetic modifications have been made to alter lipid attachment, secondary structure and to insert photoactive azobenzene moieties for active control over coiled coil…

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Promotie

Promotor: Prof.dr. T. Schmidt, Co-Promotor: S.J.T. van Noort

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Promotores: Prof.dr. J. A. Bouwstra, Prof.dr. W. Jiskoot

De missie van het Plant Sciences onderzoeksprogramma is om bij te dragen aan de duurzame productie van gewassen van hoge kwaliteit, bloemen en hoogwaardige producten met een biologische basis. Dit wordt gerealiseerd door het opdoen van fundamentele kennis over biologische processen omtrent de ontwikkeling…

Menselijke maatregelen om leeuwen te beschermen, hebben impact op de genetische gezondheid van de populaties. Dat ontdekten Leidse en Keniaanse wetenschappers door het DNA van 171 Keniaanse leeuwen te analyseren. ‘Door bijvoorbeeld reservaten te omheinen, neemt de kans op inteelt toe.’ Met de kennis…

Promotor: Prof.dr. J.P. Abrahams, Co-Promotor: N.S. Pannu

In een vernieuwende studie hebben Radboudumc en LUMC gezamenlijk een kandidaat-vaccin getest op basis van een genetisch verzwakte malariaparasiet. De resultaten van deze klinische trial, gepubliceerd in Science Translational Medicine, laten zien dat het vaccin veilig is en een afweerreactie opwekt tegen…

The studies presented in the work show the potential of the integrative use of biophysical data in defining the structural basis of protein interactions.

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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…

The chemical and structural heterogeneity of toxoid vaccines makes their analysis challenging. However, detailed insights on a molecular level can be obtained by mass spectrometry.

Het belang van taal voor zelfregulatie en sociaal gedrag bij kinderen met een extra X chromosoom

We describe certain birational modifications of nodal relative curves over a regular base of arbitrary dimension.

Leeuwen in West- en Centraal Afrika verschillen opvallend van leeuwen in het oosten en zuiden van Afrika. Dat blijkt uit genetisch onderzoek door wetenschappers van het Institute of Environmental Sciences en het Instituut Biologie Leiden. Ze werkten samen met onderzoekers van verschillende universiteiten.…

Diacylglycerol lipases (DAGLα and DAGLβ) are responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain and peripheral tissues. Selective DAGLβ inhibitors have been proposed as a potential treatment for inflammatory diseases with reduced potential for central…

The ongoing increase in antimicrobial resistance combined with the low discovery of novel antibiotics is a serious threat to our health care.

Deze longitudinale studie is gericht op ontwikkelingsrisico’s bij jonge kinderen met XXY, XXX, XYY, in de leeftijd van 1 tot 6 jaar. Het doel van het onderzoek is zicht te krijgen op de factoren die bijdragen aan risico op gedragsproblemen en psychopathologie.

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De hersenontwikkeling van kinderen met een extra X chromosoom in vergelijking met kinderen met idiopathisch autisme: inzicht vanuit MRI onderzoek

Hoe werken post-translationele eiwitmodificaties—chemische veranderingen van eiwitten nadat ze zijn gemaakt—samen om DNA te herstellen, en hoe kan dit ons helpen ziektes te begrijpen?

Nicotinamide adenine dinucleotide (NAD+) is the substrate used for the introduction of the ubiquitous and highly dynamic PTM in which either one or multiple adenosine diphosphate ribose (ADPr) moieties are covalently attached to a nucleophilic side chain of an specific amino acid in the target protein…

Promotor: G. A. van der Marel, Co-promotor: D. V. Filippov

An objective of this research was to achieve direct, well-defined and non-rate-limiting electron transfer between respiratory enzymes and the electrode surface by means of 'Q-wires'.

This Thesis describes the design, synthesis and evaluation as glycoprocessing enzyme inhibitors of focused libraries of iminosugars.

The aim of this thesis is to develop and study a robust and adaptable scaffold for supramolecular polymer self-assembly in water.

This dissertation contains four works during my PhD. Different biomaterials have been designed based on coiled-coil peptides. These biomaterials have a range of applications, inclusing drug delivery, cell sorting to cell-cell fusion.

The inverse electron demand Diels-Alder (IEDDA) pyridazine elimination emerged in 2013 as a new bioorthogonal reaction and constitutes a prime example of what is now known as dissociative bioorthogonal chemistry. The research described in this Thesis aims to develop synthetic strategies which enable…

The theoretical explanation of cosmic acceleration is nowadays one of the biggest puzzles in cosmology.

Freshwater and brackish water ecosystems are arguably the most vulnerable ecosystems on earth, due to concentrated human developments in and around them. The Pontocaspian (PC) region located at the border of Europe and Asia contains a variety of brackish water ecosystems and unique inhabitants, known…

Promotor: A. Kros

This thesis advances our understanding of lipid uptake, a vital first step in lipid metabolism, by developing innovative click chemistry-based tools to study how immune cells internalize lipids.

The research described in this thesis focused on the use of bioorthogonal antigens to investigate immunological processes in antigen presenting cells. Bioorthogonal antigens are antigenic proteins produced through recombinant expression in a methionine auxotrophic E. coli strain.

This thesis describes the design and development of subunit‐selective inhibitors of particular catalytically active subunits of human constitutive proteasomes and immunoproteasomes.

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…

Stochastic resetting is simple enough to be approached analytically, yet modifies stochastic processes in a non-trivial way.

Promotor: P.D. Grünwald

Promotor: Prof.dr. P. Stevenhagen

Promotor: Johan Kuiper, Co-promotor: Saskia C.A. de Jager

In summary, the collective results described in this thesis show that nanoparticulate vaccines can be delivered intradermally by coated and hollow microneedles and evoke antigen-specific immune responses.

The goal of the research presented in this thesis was to explore the chemical space of ruthenium(II) photocages, investigate their ability to host potent chemotherapy drugs, and to red shift the activation wavelength of the most promising PACT candidates to conduct biological studies.

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.