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,…

The ambition of the Medical Systems Biophysics and Bioengineering group led by Alireza Mashaghi is to develop and use physics and engineering concepts and tools for pathophysiology, diagnostics and therapy.

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…

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

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.

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

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

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…

Viral hemorrhagic fever (VHF) is a group of acute diseases caused by highly infectious viruses including Ebola, Lassa, Dengue viruses. Its high mortality rate poses high risk to public health, however, studies on VHF have been hampered due to the non-availability of proper models and incomplete knowledge…

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

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

The long term goal of the Biophysical Organic Chemistry/SSNMR group, headed by Prof. Huub de Groot, is to reach an understanding of structure, dynamics and functional mechanisms of membrane proteins and self-organized biological assemblies and to translate this knowledge into new concepts for nano-devices,…

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.

This dissertation combines the use of defined microenvironments, high-resolution fluorescence microscopy, and time-resolved analysis, to study intracellular and cellular motility.

Human cells are protecting their proteins from unfolding and aggregating. That's what biophysicist Alireza Mashaghi and his team discovered after seven years of in-depth research into the folding mechanisms of proteins. With an unprecedented approach, the team was able to study the folding of a single…

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,…

Optical detection of a single electron using a single molecule has never been done. Leiden physicist Michel Orrit and his team have now identified a molecule that is sensitive enough to detect an electron at a distance of hundreds of nanometers. The results are published as a cover article in ChemPh…

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.

Promotor: A. Kros

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

Mechanobiology is a major area in biology, however, mechanics is currently a missing element in drug development pipelines. This has led to a high cost for the society. Mechanotoxicity of drugs often appears as a long-term side effect of drugs, and has led to removal of drugs from the market. Furthermore,…

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

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.

Leiden University has appointed John van Noort as Professor in Biophysics. He studies the way in which our DNA is folded and read out.

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

Mashaghi lab conducts research at the interface of physics, engineering and biomedicine. We develop and use theoretical and experimental approaches to address basic and applied research problems.

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.

Physics and Engineering Approaches to Biomedicine and Pharmacology

The editors of Biophysical Journal have selected a publication from Daniela Kraft’s group as the Paper of the Year 2017. The award recognizes an outstanding contribution by a young investigator.

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

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

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.

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).