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.

The research described in this thesis combines the latest insights in lysosomal function with lysosome centred cell signalling.

Lysosomal storage disorders (LSDs) are a group of orphan diseases characterized by lysosomal dysfunction or impaired lysosomal catabolism and affect collectively about 1 in 5000 live births.

Lysosomal glycosidases are acid hydrolases that fragment glycoconjugates in lysosomes.

Overkleeft

The company Azafaros was established in 2018 to translate innovative science from Leiden University and Amsterdam University Medical Center into novel disease-modifying treatment modalities for rare genetic metabolic disorders such as lysosomal storage diseases.

Science, Institute of Biology Leiden (IBL)

Advanced mass spectrometry of glycosphingolipids takes the central stage in this thesis. Investigations focus on characterization of glycosphingolipid metabolism in health and disease with emphasis to the detection and accurate quantitation of known and so far unknown glycosphingolipids and closely…

Through metabolism, biochemical processes give rise to the complexity of life. Acquired and inborn errors in metabolism underlie many diseases occurring in man. The challenge for present day medical biochemistry is to find, and integrate, pieces of information at molecular, cell and organismal level…

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

The sustainable demolition of the Gorlaeus high-rise of the Faculty of Science is now complete. This demolition is part of the redevelopment of the faculty. A part of the steel construction will form the basis of a new green bike park.

A part of the steel construction of the former Gorlaeus high-rise will form the basis of a new green bike park which is part of the redevelopment of the Faculty of Science.

Obtaining imaging data is nowadays only the start of your project. Once the data has been acquired there are many things that still need to be done.

Through metabolism, biochemical processes give rise to the complexity of life. Acquired and inborn errors in metabolism underlie many diseases occurring in man. The challenge for present day medical biochemistry is to find, and integrate, pieces of information at molecular, cell and organismal level…

Leiden biotech startup Azafaros has successfully completed a funding round, raising 25 million euros of investments for developing treatments of rare metabolic disorders. The company holds exclusive license to a library of novel patented compounds discovered by experts from Leiden University.

Deficiency of glucocerebrosidase (GBA) underlies Gaucher disease, a common lysosomal storage disorder. Carriership for Gaucher disease has recently been identified as major risk for parkinsonism. Presently, no method exists to visualize active GBA molecules in situ. We here report the design, synthesis…

Medical Biochemistry is a section of the Leiden Institute of Chemistry at Leiden University. The section is headed by Prof. Dr. Hans Aerts.

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

The Hydrogen network brings together leading researchers from different disciplines and sectors with a combined expertise that maximises the chance of achieving scientific breakthroughs in production and storage of hydrogen, while guaranteeing the successful training of a new generation of scientists…

Social anxiety runs in families, but the neurobiology underlying this genetic vulnerability is until now largely unknown. The unique Leiden Family Lab study on Social Anxiety Disorder (LFLSAD) aims to broaden our knowledge with respect to this genetic susceptibility.

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Although exposure therapy is the gold-standard treatment of posttraumatic stress-disorder (PTSD), only half of the patients adequately benefit from it. Based on recent insights into the mechanisms of extinction, this project examines strategies and techniques to improve exposure treatment outcome in…

The precise psychobiological mechanisms leading to chronic physiological stress responses have not been sufficiently explained, although stress is a major risk factor for disease and early death. A problem for conventional stress theory is that most of these responses seem to occur in situations without…

How to come to valid risk stratification of alcohol use disorder?

One of the current research projects funded by the profile area Political Legitimacy is the research group From Disorder to Order: Conflict and the Resources of Legitimacy.

This thesis is devoted to an in-depth examination of the various effects of disorder in the cuprate high-temperature superconductors.

The key question addressed in this family study is whether the psychophysiological and neurocognitive abnormalities often reported in SAD patients are heritable and can thus be found in family members of SAD patients as well. Determination of heritability of these deficiencies is essential for endophenotyping.…

How can we develop new chemical biology tools and approaches to understand and interfere with glucosylceramide metabolism in relation to Gaucher disease?

The studies described in this thesis deal with glycosidases, in particular alpha-galactosidases.

How does stress affect different components of behavioral impulsivity and aggression in patients with Borderline Personality Disorder compared to clinical controls (patients with Attention Deficit Hyperactivity Disorder) and healthy controls?

Why do children with an Autism Spectrum Disorder (ASD) have difficulties with acquiring emotion regulation skills; and how is this related to their social impairments and comorbid psychopathology?

The current hepatitis B vaccines need to be stored and transported under refrigerated conditions (2-8 degrees C). This dependence on a cold-chain is highly challenging in areas where hepatitis B virus infections are endemic.

How do dissociative states affect the ability to suppress emotional distraction (in the context of a working memory task) in patients with Borderline Personality Disorder?

Does an Emotional Working Memory Training show a beneficial transfer effect on emotion regulation (reappraisal) capacities in patients with Borderline Personality Disorder?

What is the role of emotion regulation in coping with interpersonal feedback?

Dissertation

Which criteria do ED patients and therapists evaluate as most relevant for recovery? Do patients and therapists differ in their evaluations? Do eating disorder patients differ from a healthy control group in their scores on the Recovery Scale?

Research projects

Researchers at Leiden University have made a breakthrough in the study of the hereditary Pompe disease. Together with colleagues in York, they have developed a molecule that binds to the enzyme that is key to the progress of the disease. The findings have been published in ACS Central Science.

Have you ever experienced the feeling of awkwardness when attending a party where you didn’t know anybody? Ever felt shy at a party within the first few minutes? While this feeling is labelled loosely as feeling socially anxious, social anxiety disorder (SAD) goes to a much further extent.

To get a feeling of how we operate at LED3 when it comes to Early Drug Discovery, please browse through our case studies. When you select a case study you’ll find relevant contacts.