Single-Molecule Microscopy (SMM) techniques constitute a group of powerful imaging tools that enable researchers to study the dynamic behavior of individual molecules.

Detecting nanoscopic objects plays an important role in nanoscience in particular, in the rapidly growing field of nanobiology. The forebear to modern super-resolution microscopy for single molecule investigation, is fluorescence microscopy.

The sequence-dependence of biomolecular interactions involving nucleic acids and proteins is essential for numerous processes inside the cell. Insights into the underlying molecular mechanisms have been obtained using various biochemical and biophysical methods on two different levels — bulk and sin…

The aim of the research presented in this thesis was to develop new methods forchallenging systems in liquid-state NMR using paramagnetic effects generated by thetwo-armed probe CLaNP-5.

In this thesis we investigated the ability of two-photon multifocal microscopy for single-molecule microscopy in live cells and organisms.

This thesis is a collection of experimental attempts to enhance photoluminescence of fluorescent molecules and quantum dots with single gold nanorods (GNRs) and relevant applications.

Since the early 1990s, one can isolate the optical signal of a single molecule and single-molecule spectroscopy has quickly grown into an important research field.

Macromolecular Biochemistry is a section of the Leiden Institute of Chemistry at Leiden University, comprising the PIs Marcellus Ubbink, Remus Dame, Lars Jeuken, Anne Wentink, Anjali Pandit, René Olsthoorn, Alia Matysik, Sebastian Geibel and Steffen Brünle.

This dissertation revolves around the design and implementation of novel instrumentation and related measurement techniques, at the single molecule level, for use in biophysical research. Chapter 1 presents an introduction to the field of fluorescence-based single molecule measurements. In particular,…

Intrigued by the way cells autonomously regulate their fate, we strive to understand and visualize cellular processes as the basis of Cell Signaling.

Spectroscopic studies on fluorescent single molecules in organic condensed matter does not only provide information about the molecule itself, but also its near environment. By suppression of phonon-induced broadening of spectral lines through cooling to low temperatures, small changes in the spectral…

Promotor: Prof.dr. M.A.G.J. Orrit

Promotores: Prof.dr. G.W. Canters, Prof.dr. T.J. Aartsma

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…

In human cells, a meter-long DNA is condensed inside a micrometer-sized cell nucleus. Simultaneously, the genetic code must remain accessible for its replication and transcription to functional proteins.

Promotor: T. Schmidt, Co-Promotor: B.E. Snaar-Jagalska

Early time-resolved experiments by Frauenfelder on the ensemble of the kinetic rebinding of CO to myoglobin molecules resulted in a stretched exponential relaxa-tion due to a very large spread of the reaction rates of individual molecules.

This thesis aims to improve the detection from ultra-weak single emitter by enhancing their emission properties with plasmonic nanostructures. We exploit the wet-chemically synthesized single crystalline gold nanorods (GNRs) as our basic frameworks in the whole studies, simply because of their unique…

Promotor: M.A.G.J. Orrit

Single-molecule spectroscopy has become a powerful method for using organic fluorescent molecules in numerous applications.

All living systems are assembled from nature’s repertoire of small, medium, and large organic molecules. This theme focuses on the study, discovery and development of novel bioactive compounds obtained from biodiversity. We aim for new insights into the role of these molecules in the natural environment,…

Ariadne Schmidt, Isabelle Devos and Julie de Groot provide you with refreshing insights concerning the study on urban singles in the period between 1200 and 1900.

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…

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

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…

Promotor: M. Ubbink, Co-promotor: G. Siegal

Microbial Sciences' contribution to the Bioactive Molecules research theme is to discover new bioactive molecules and enzymes and unravel their mechanisms of action, regulatory networks, and the (bio)synthetic pathways required for their production.

Plant Sciences' contribution to the Bioactive Molecules research theme is to identify new plant bioactive molecules, and unravel their mechanisms of action in plant development or health, and the regulatory networks and (bio)synthetic pathways required for their production.

The single cell group (SCG) is part of the Metabolomics & Analytics Centre Our research is centered around developing innovating analytical methods tailored for small-volume, or single cell analysis to enable metabolomics-driven systems biology in personalized health strategies. We are always on…

On 14 December, Jouke Tegelaar defended the thesis 'Single supervision, single judicial protection? Towards effective judicial protection in Single Supervisory Mechanism composite procedures'. The doctoral research was supervised by Matthias Haentjens and Willemien den Ouden.

Animal Sciences’ contribution to the Bioactive Molecules research theme includes research on molecules from natural sources, such as plants, insects, and snake venom, with the aim to identify novel anti-cancer, anti-inflammatory, anti-microbial, and anti-diabetic agents.

Complex Organic Molecules (COMs) have been detected in objects across different stages of stellar evolution.

We study cell-fate decision-making using embryonic stem cells as a model system. Stem cells integrate a large number of cues to direct their development into a great variety of cell types.

In this work, we investigate the minute circular dichroism effects of single nanoparticles.To this aim, we apply photothermal imaging with a polarization-modulated heating beam.

Promotor: M. Ubbink, Co-promotor: G. Siegal

This thesis revolves around the electronic spectroscopy of molecules in the laboratory and the search for the carriers of the diffuse interstellar bands (DIBs).

Promotor: Prof.dr. E. F. van Dishoeck, Co-promotor: A. N. Heays

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).

While bioinformatics methods deal with the analysis of sequence information (be it proteins or DNA), the field of cheminformatics is concerned with the analysis of small-molecule datasets.

Nucleoid associated proteins maintain the architecture of the bacterial chromosome and regulate gene expression, hinting that their role as transcription factors may involve local three-dimensional chromosome re-modelling.

Large areas of space are filled by molecular clouds that consist of gas and dust grains that are the remnants of dead stars. When these clouds start collapsing, the decreasing temperature and increasing density cause gas particles to start accreting onto dust grain surfaces.

The main focus of the thesis is the discovery and development of novel inhibitors of bacterial metallo-β-lactamases (MBLs).

MHC class I and MHC class II molecules present peptides to the immune system to drive proper T cell responses. Pharmacological modulation of T-cell responses can offer treatment options for a range of immune-related diseases.

Promotor: M. Ubbink, Co-promotor: G. Siegal

I will give a general introduction to the field of molecular electronics, its history, methods and challenges. I will also introduce the subject of my investigation and provide a brief outlook to the remainder of our thesis.

Promotor: Prof.dr. J. Brouwer, Co-promotor: Dr. Remus Th. Dame

Heterogeneous catalyzed processes are highly significant to the chemical industry. Dissociative chemisorption (DC) of molecules on surfaces is always considered as a step with a high degree of rate control for heterogeneous catalysis.

This perspective addresses four challenges facing theorists whose aim is to make quantitatively accurate predictions for reactions of molecules on metal surfaces, and suggests ways of meeting these challenges, focusing on dissociative chemisorption reactions of H2, N2, and CH4.