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

Diacylglycerol lipases (DAGLα and DAGLβ) convert diacylglycerol to the endocannabinoid 2-arachidonoylglycerol. Our understanding of DAGL function has been hindered by a lack of chemical probes that can perturb these enzymes in vivo.

The lipid membrane is a basic structural component of all living cells. Embedded in this nanometer-thin barrier, membrane proteins shape the membrane and at the same time respond to the shape of the membrane.

This thesis systematically analyzes the physical-chemistry of lipid-graphene interactions with the major objective of reconciliating the variety of results reported in the literature.

Like a mixture of oil and water, lipid membranes separate into two liquid phases.

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

The skin protects the body from unwanted influences from the environment as well as excessive water loss. The barrier function of the skin is located in the stratum corneum (SC).

Our in-house human skin equivalents contain all stratum corneum (SC) barrier lipid classes, but have a reduced level of free fatty acids (FAs), of which a part is mono-unsaturated. These differences lead to an altered SC lipid organization and thereby a reduced barrier function compared to human skin.…

The lipid matrix in the stratum corneum (SC), the upper layer of the skin, plays a critical role in the skin barrier. The matrix consists of ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs).

Source: International Journal of Cosmetic Science, Volume 37, Number 1, pp. 148-148 (2015) ISBN: 0142-5463

The skin is our natural barrier and lipids are a key part of this barrier. In the outer skin layer, the stratum corneum (SC), lipids form a densely organized structure dependent on the composition of these lipids.

How are the epidermal lipid pathways involved in health and disease.

There is considerable need for improved skin models to develop safe and efficient drugs for skin delivery as well as for cosmetic and chemical product testing on the skin.

The skin barrier function is provided by the stratum corneum (SC). The lipids in the SC are composed of three lipid classes: ceramides (CERs), cholesterol (CHOL) and free fatty acids (FFAs) which form two crystalline lamellar structures. In the present study, we investigate the effect of CER chain length…

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

Cardiovascular diseases are among the most frequent causes of death in the world. The main underlying pathology of cardiovascular diseases is the development of atherosclerosis in the medium and large-sized arteries.

Source: International Journal of Cosmetic Science, Volume 37, Number 1, pp. 158-158 (2015) ISBN: 0142-5463

Source: Journal of Investigative Dermatology, Volume 135, pp. S59-S59 (2015)

The barrier function of the skin is primarily provided by the stratum corneum (SC), the outermost layer of the skin. Skin barrier impairment is thought to be a primary factor in the pathogenesis of atopic eczema (AE).

The outermost layer of the skin, the stratum corneum (SC), is responsible for the skin barrier function, protecting the body from pathogens, chemicals and other unwanted substances from the external environment. The SC lipid matrix provides the only continuous pathway through the SC and is considered…

It is the aim of this project to better understand how the physical properties of lipids influences the structure and overall barrier function of the skin.

Netherton Syndrome (NTS) is a rare genetic skin disease caused by mutations in the serine protease inhibitor Kazal-type 5 gene, which encodes the lympho-epithelial Kazal-type-related inhibitor. NTS patients have a profound impaired skin barrier function. Because SC lipids play a crucial role in the…

This paper describes two synthetic lipid models designed to replace human stratum corneum (SC) in studies of the impact of volatile organic chemicals on the molecular organization of the skin barrier lipids.

The lipid matrix of the skin's stratum corneum plays a key role in the barrier function, which protects the body from desiccation. The lipids that make up this matrix consist of ceramides, cholesterol, and free fatty acids, and can form two coexisting crystalline lamellar phases: the long periodicity…

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

Cell adhesion signaling

Alexander Kros and co-workers describe how mesoporous silica nanoparticles (MSNs) are delivered into cells via membrane fusion thereby omitting endocytosis pathways. Fusion is induced by a pair of complementary coiled-coil lipopeptides inserted into the membrane of cells and in the bilayer of lipid-coated…

Who benefits from CXCR/CXCL chemokine signaling during infection: host or pathogen?

The PID-directed shift in PIN polarity has been broadly accepted as one of the essential mechanisms for the regulation of auxin transport polarity.

Ceramides (CERs), cholesterol, and free fatty acids (FFAs) are the main lipid classes in human stratum corneum (SC, outermost skin layer), but no studies report on the detailed analysis of these classes in a single platform.

Promotor: H.P. Spaink, A.H. Meijer Co-promotor: R. Marin-Juez

The effectiveness of the skin barrier underlies the outer layer of the skin: the stratum corneum (SC). However, in several skin diseases this barrier is impaired. In two inflammatory skin diseases, atopic eczema and Netherton syndrome, an increased level of monounsaturated fatty acids (MUFAs) has been…

OBJECTIVES: To determine whether the lipid/protein ratio and the total dry SC mass per surface area are related with the skin barrier function of controls and AE patients.

Promotores: A.H. Meijer, H.P. Spaink

Promotor: Prof.dr. P. Hooykaas, Co-promotor: Dr. R. Offringa

In previous studies at our laboratory it was demonstrated that drug exposure of HepG2 cells can lead to an altered TNFα-induced NF-κB oscillatory phenotype, concurrent with a synergistically increased sensitivity for TNFα-induced apoptosis.

Source: British Journal of Dermatology, Volume 170, Number 6, pp. E18-E19 (2014) ISBN:0007-0963

Bacteria are highly complex and diverse organisms that have adapted to survive in ecological niches ranging from the most extreme to the most heterogeneous environments.

PhD Defence

1. What is the exact role of PIN proteins in PAT? 2. How is PIN polarity established, and how is it modulated by AGC kinase-mediated phosphorylation? 3. What is the role of the AGC kinase, as modulators of PAT, in translating environmental signals, such as gravity, light or mechanical stress, to plant…

PhD Defence

Establishing human induced pluripotent stem cell (iPSC) CRISPR-Cas9-based fluorescent reporter cell lines for NF-kB signalling. We will use this to enable studying the dynamic activation and downstream signalling of Toll-like receptor and cytokine signalling in iPSC-derived differentiated cells in a…

This project is funded by the Dutch Cancer Society. The project will be part of an ongoing research line aimed at identifying mechanisms of cancer therapy resistance and metastasis. In this project, it will be investigated how the Grainyhead family of transcription factors controls therapy response…

This thesis focuses on the role of chemokine receptors CXCR3 and CCR2 in the inflammatory process and infection control using the zebrafish model.

The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB2R, their selectivity, molecular mode of action and pharmacokinetic properties have…

Handbook of Signal Processing Systems is organized in four parts. The first part motivates representative applications that drive and apply state-of-the art methods for design and implementation of signal processing systems; the second part discusses architectures for implementing these applications;…

Source: Mol Psychiatry (2015)

On November 1st, Min Liu succesfully defended her doctoral thesis and graduated. The Leiden University Centre for Linguistics congratulates Min on this great result.

This thesis considers multi-prover commitment schemes whose security is based on restrictions on the communication between the provers.