Over de sporen die Darwin, hoewel nooit in Leiden geweest, er toch achterliet.

The present thesis focuses on the pharmacological concept of drug-target interaction, which dates back to the beginning of modern pharmacology.

In eight chapters, the thesis of Rafaël Vos covers the effect of temperature and pressure on the electrochemical CO2 reduction.

The cellular metabolism of immune cells constitutes an important part of their proper function and activation. Using T cells as an example, this phenomenon is highlighted by the metabolic reprogramming that occurs in these cells upon activation.

The main goal of the research described in this thesis was the development of new photoactivated chemotherapy (PACT) ruthenium(II) complexes bearing a non-toxic photolabile ligand.

This thesis describes the synthesis and biological evaluation of TLR2/6, TLR4, TLR7/8 and TLR9 ligands, of which the activity can be conditionally controlled.

Promotor: A. Kros, Co-promotor: R.R.C.L. Olsthoorn

Despite the fact that gold nanoparticles (GNPs) are one of the most studied nanoparticles, there is still a necessity for new approaches allowing for effective protective coating to enable wider use of GNPs in biomedical applications.

In this thesis, we aimed to better understand the underlying mechanisms involved in TNBC progression and metastasis formation and discover new targets to reduce breast cancer related deaths.

In this thesis, we used genetically engineered mouse models and a variety of cell-culture based assays to identify genes and pathways that are involved in the development and treatment of invasive lobular carcinoma (ILC).

Metastasis is responsible for over 90% of cancer-related deaths and arises from the ability of a small subset of tumor cells to detach from the primary tumor, overcome multiple biochemical and mechanical barriers, disseminate through the body, and colonize distant organs.

Over several decades, a variety of computational methods for drug discovery have been proposed and applied in practice. With the accumulation of data and the development of machine learning methods, computational drug design methods have gradually shifted to a new paradigm, i.e. deep learning methods…

Promotor: A.P. IJzerman Co-promotor: L.H. Heitman

Behandelmethoden voor chronische ziekten zijn beperkt. Artsen en onderzoekers van het Leids Universitair Medisch Centrum (LUMC) en de Universiteit Leiden werken aan nieuwe therapieën als alternatief voor orgaantransplantatie. Doel is om organen te herstellen in hun oorspronkelijke functie en op die…

The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.

Solute carrier (SLC) transporters are a large and diverse class of relatively understudied transmembrane proteins.

Shape and biological function are tightly connected. Physical descriptions are used to connect the shape of a biological system with its function.

Tijdens de viering van de 54ste Dies Natalis van Universitas Padjadjaran in Bandung, Indonesië, zijn op 9 september 2011 onderscheidingen uitgereikt aan de Leidse prof.dr. L.J. Slikkerveer en drs. L.E.H. Vredevoogd. Zij kregen deze voor hun uitzonderlijke bijdrage aan de succesvolle wetenschappelijke…

Drug development critically depends on preclinical models that mimic human physiology, yet traditional two-dimensional cultures and animal models often lack predictive power.

Promotor: B. van de Water

This thesis investigates how cell shape and collective behavior influence the dynamics and structure of biological tissues, which are crucial for understanding processes like embryonic development, tissue regeneration, and metastasis.

Mechanical forces are known to play an important role in bacterial colonies. In this dissertation, we study the self-organization at various stages of growing bacterial colonies, and focus on the mechanical effects of cell growth.

Cardiovascular diseases are a leading cause of death worldwide, and better models are urgently needed for disease progression studies and drug development.

Promotor: B. van de Water

Image-Pro Plus, ImageJ, Cell Profiler, R, Knime en NIS-elements

This thesis seeks to investigate how cancer-associated mutations affect the pharmacological properties of selected GPCRs—primarily A2AAR and 5-HT2CR—through a combination of ligand binding assays, signaling readouts, kinetic profiling, and cellular functional assays.

Promotor: Huub J.M. de Groot, Co-promotor: Francesco Buda

De nieuwe software van Microsoft, VALL-E hoeft maar drie seconden van een stem te horen om hem bijna foutloos te kunnen imiteren. Je kunt zelf kiezen welke emotie de stem moet gebruiken en wat hij moet zeggen. Valerie Frissen, Hoogleraar Digitale Technologie en Sociale Verandering bij eLaw en directeur…

Integrins play an essential role in multicellular life by connecting cells to the extracellular matrix.

Image segmentation is a fundamental task in computer vision, with applications ranging from medical diagnostics to archaeological research.

The first steps are made in personalised cancer vaccination strategies, which aim to induce a more specific immune response with fewer side effects. The activation of cytotoxic T cells is crucial for an effective immune response.

Endothelial dysfunction and microvascular diseases are key drivers of cardiovascular disease, the world's leading cause of death.

The overarching goal of this thesis is to set the foundations, but also make the first essential steps towards establishing a comprehensive, mesoscopic, hydrodynamic theory of epithelial tissues. The stage is set by an exhaustive study of topological defects in passive p-atic liquid crystals, singularities…

Cholesterol influences many pathways, including serving as precursor for adrenal steroidogenesis. Imbalance of cholesterol levels has been implicated in several diseases including cardiovascular diseases and its underlying pathology, atherosclerosis.

Drug development is hampered by the limited predictive value of conventional 2D culture systems, which fail to recapitulate the complexity of the disease microenvironment and contribute to high clinical attrition rates.

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.

In this thesis, we focus on novel proteins/mechanisms that regulate integrin-adhesion mediated mechano-transduction.

This doctoral thesis is an effort to understand how lipid phase-separation induced by diacylglycerol analogues in lipid-based nanoparticles affects their in vivo behavior, leading to specific nanoparticle-protein communications and selective cell targeting.

In photoactivated chemotherapy (PACT), a biologically active compound is caged by a light-cleavable protecting group.

Pericytes, the mural cells of blood microvessels, are important regulators of vascular morphogenesis and function that have been postulated to mechanically control microvascular diameter through as yet unknown mechanisms.

This thesis focuses on the synthesis, characterization and performance towards CO2 electroreduction of mono and bi-metallic particles based on p-block metals

During the development of the (human) body from a single fertilized egg, organs and structures must form. The development and growth of biological forms is called morphogenesis.

De keten die patiënten voorziet van nieuwe medicijnen, bestaat uit diverse complexe schakels: van fundamentele wetenschap, tot klinische tests, tot productie. Deze hele keten is aanwezig in Leiden. De Universiteit Leiden, het Leids Universitair Medisch Centrum (LUMC) en de bedrijven op het Leiden Bio…

Wat is het persoonlijke verhaal van wetenschappers als Einstein, Kamerlingh Onnes en Swammerdam? Een aantal Leidse honoursstudenten heeft een virtuele tentoonstelling opgezet om de mensen achter de ontdekkingen weer te geven.

This thesis describes the synthesis, analysis of various tetrazine bearing compounds and use in bioorthogonal chemistry.

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.

The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.