Drug Discovery Sciences

Deciphering drug-target interactions at the molecular level

Overview: The Molecular Pharmacology specialisation within the DDS Master's programme delves into the intricate mechanisms by which drugs interact with biological systems at the molecular and cellular levels. This track equips students with a profound understanding of receptor pharmacology, signal transduction pathways, and the molecular basis of drug efficacy. Emphasising both theoretical knowledge and practical skills, the programme prepares graduates to contribute to the development of novel therapeutics and the optimisation of existing drug therapies.

Core learning objectives:

• Molecular mechanisms of drug action: Gain in-depth molecular understanding of how drugs (small molecules and biologics) interact with their targets, including G protein-coupled receptors (GPCRs), ion channels, receptor tyrosine kinases, nuclear receptors, and enzymes. Investigate the molecular basis of drug efficacy, side effects, and resistance mechanisms.
• Signal transduction pathways: Explore the biochemical aspects of cellular signaling cascades in both health and disease, and identify opportunities to modulate these processes by drug-target interactions.
• Pharmacodynamics and Pharmacokinetics: Learn the principles governing the effects of drugs on the body (pharmacodynamics) and the body's effects on drugs (pharmacokinetics), including absorption, distribution, metabolism, and excretion (ADME).

Hands-on experience with state-of-the-art technologies: The Molecular Pharmacology track emphasises practical training using advanced instrumentation and methodologies:

• Drug modalities: work with small molecule synthetic compounds, biologics (nanobodies and venoms), and (cyclic) peptide/protein ligands, and gain experience in their selection/modification/optimisation processes.
• Cell-based assays: Conduct experiments using cultured cells to assess drug effects on cell viability, proliferation, and signaling pathways.
• Binding studies: Perform binding assays to determine drug affinity and association/dissociation binding kinetics using radioactively and fluorescently labeled ligands.
• Functional assays: Utilise biochemical and biophysical approaches to evaluate receptor activation and downstream effects using bioluminescence- and fluorescence-based biosensors in real time. Identify relevant signaling networks to design and develop biosensor assays using high-end microplate readers and (high content) imaging.
• Molecular biology and biochemistry techniques: Apply methods like PCR, Western blotting, and immunocytochemistry to study protein expression and post-translational modifications.

Career prospects: Graduates are well-prepared for roles as molecular pharmacologists in pharmaceutical companies, biotechnology firms, and regulatory agencies. Their expertise in molecular mechanisms of drug action positions them to contribute to drug discovery, development, and safety evaluation. They are also well-equipped to continue their career as research scientists in academia.

Ideal candidates: This specialisation is designed for students with a BSc or BASc background in medicinal chemistry, biochemistry, pharmacology, molecular biology, cellular biology, or related fields, and a keen interest in understanding the molecular basis of drug actions. A commitment to scientific research and a passion for innovation in therapeutic discovery (or development) are essential qualities for prospective students.

Programme curriculum highlights: Students in the Molecular Pharmacology specialisation gain expertise in advanced pharmacological concepts and techniques. Key compulsory courses in this specialisation cover:

• Advanced pharmacology: Focusing on the molecular basis and quantification of drug-target interaction and modulation of cellular responses.
• Drug Target Biochemistry and Signaling: Explores the pathways and networks involved in cellular responses to drugs.
• ADME: Covers the processes affecting drug disposition and the implications for therapeutic efficacy and safety (pharmacokinetics and drug metabolism).
• Research skills and scientific communication: Development of essential research skills, including experimental design, data analysis, and effective communication of scientific findings.

Additionally, students complete a Major Research Project (42-60 ECTS), allowing them to conduct in-depth research in academic or industrial settings.

Research internship opportunities: Students have access to diverse research projects, both within the university and through external collaborations. Examples of internal research internship opportunities include:

1. Investigation of GPCR signaling in cellular models: Studying the role of GPCRs in pathophysiological cellular regulation and identifying potential therapeutic targets.
2. Pharmacological evaluation potential drug candidates (small molecules and biologics (nanobodies)): Assessing the efficacy, potency, and selectivity of new drug candidates using various in vitro models.

External internships may be undertaken at pharmaceutical companies, research institutes, and academic hospitals, providing exposure to translational research and clinical applications of pharmacological principles.

Synthesis of Drugs: making biologically active molecules come to life

Overview: In the specialisation Synthesis of Drugs, you will focus on the organic chemistry of biologically active compounds, peptides/peptidomimetics, radiolabeled molecules or synthetic methodologies. You will work with the newest synthesis, purification and compound characterisation equipment. Your classes will reveal how to reap the fruits of life science research and will guide you along the way to become an innovative organic chemist in a life science context.

Core learning objectives:

• Synthetic planning: Plan efficient synthesis routes to your designed molecules
• Synthetic reactions: Utilise the toolbox of organic reactions to get your target molecule
• Chemical analysis: Learn all about the latest techniques to confirm the identity and purity of your synthesised molecules
• Drug context: get acquainted to and operate in the various chemical-biology, medicinal chemistry and diagnostic contexts that organic molecules are studied in

Hands-on experience with state-of-the-art technologies: the Synthesis of Drugs track emphasises practical training using advanced instrumentation and methodologies:

• Synthesis planners: Professional software that is key for efficient planning of synthesis routes
• Synthesis: Perform synthesis experiments with a variety of techniques (thermal chemistry, electrochemistry, photochemistry, microwave heating and/or radiolabeling)
• Analysis: Utilise techniques such as 2D NMR spectroscopy, chromatography and mass spectrometry

Career prospects: Graduates are well-prepared for roles as organic chemists in pharmaceutical companies, fragrance companies, biotechnology firms, government institutes, etc as well as in non-research related jobs in education, policy, etc. Their expertise in synthetic chemistry positions them well to contribute to drug discovery and development. They are also well equipped to continue their career as research scientists in academia.

Ideal candidates: This specialisation is designed for students with a strong background in organic chemistry and with a keen interest in understanding and exploring the role of organic chemistry in drug research, chemical biology and diagnosis. A strong commitment to a research-oriented context and a passion for innovation in drug discovery are essential qualities for prospective students.

Programme curriculum highlights: Students in the Synthesis of Drugs specialisation become experts in advanced organic chemistry concepts and techniques, and become well-rounded team players in a drug research context. Key compulsory courses in this specialisation cover:

• Physical Organic Chemistry: Focuses on the physical-chemistry concepts that are essential for understanding and exercising organic synthesis.
• Spectroscopic Approaches: Explores the various techniques key in safeguarding identity and purity of synthesised molecules, with an emphasis on advanced 2D NMR spectroscopy.
• Synthetic Approaches: Covers the toolbox of organic reactions that drug researchers have at their disposal to prepare biologically interesting organic molecules.
• (Where applicable) Principles of Drug Targets and Principles of Drug Discovery: learn the fundaments of computer-aided drug design, molecular pharmacology and molecular toxicology necessary for efficiently operating in interdisciplinary research teams
• Research skills and scientific communication: Development of essential research skills, including experimental design, data analysis, and effective communication of scientific findings.

Additionally, students complete a Major Research Project (42-60 ECTS), allowing them to conduct in-depth research in academic or industrial settings.

Research internship opportunities: Students have access to diverse research projects, both within the university and through external collaborations. Examples of internal research internship opportunities include:

1. New reaction methodologies: Find new reaction types that excel in performance and yield, and deliver novel interesting scaffolds
2. Medicinal chemistry: Synthesise molecules that are designed to bind a biological target hypothesised to be of relevance in a disease area
3. Radiochemistry: Use organic chemistry to label molecules with isotopes for potential use in PET and other diagnostic techniques
4. Protein chemistry: Chemically alter peptides or peptidomimetics to make new drug modalities

External internships may be undertaken at pharmaceutical companies, research institutes, and universities, providing exposure to various research settings and possibly translational research.

Molecular Toxicology: Deciphering the molecular basis of toxicity

Overview: The Molecular Toxicology specialisation within the Drug Discovery Sciences (DDS) Master's programme offers an in-depth exploration of the cellular stress responses and the molecular mechanisms underlying the toxic effects of chemical substances, focusing on pharmaceuticals, but also paying attention to food additives and contaminants, environmental pollutants, and industrial chemicals. This track equips students with the knowledge and skills to assess and predict toxicological outcomes, contributing to the development of safer therapeutic agents and the protection of public health. By integrating theoretical knowledge with practical experience, the programme prepares graduates to address complex challenges in toxicology and environmental health sciences.

Core learning objectives:
Mechanisms of toxicity: Gain a comprehensive understanding of how chemicals induce adverse effects at the molecular and cellular levels, including activation of cellular stress response pathways (e.g. oxidative stress, unfolded protein response, DNA damage, apoptosis, and carcinogenesis, inflammation).

• Toxicokinetics and Toxicodynamics: Study the absorption, distribution, metabolism, and excretion (ADME) of toxicants, and how these processes influence the intensity and duration of toxic effects.
• Risk assessment and regulatory toxicology: Learn to evaluate the potential health risks associated with chemical exposures, develop risk assessment models, and understand the regulatory frameworks governing chemical safety.
• In Vitro toxicology and advanced human cell systems: Acquire proficiency in using  human cell-based assays to predict toxicological outcomes, reducing reliance on animal testing and enhancing the efficiency of safety evaluations (New Approach Methodologies, NAMs) that focuses on animal free methods. Learn more about advanced human cell models, including induced pluripotent stem cells (iPSC), organoids and organ-on-a chip.

Hands-on experience with state-of-the-art technologies: The Molecular Toxicology track emphasises practical training using advanced instrumentation and methodologies:

• Cell culture and High-Throughput Screening: Cultivate various cell models (cell lines, primary cells, iPSC-derived cells) to assess toxicological endpoints (enzymatic assays, fluorescent reporter cell lines, oxygen consumption rate & mitochondria toxicity) and transport assays (uptake and efflux of xenobiotics).
• Advanced imaging techniques: Apply fluorescence microscopy, confocal microscopy, and live-cell imaging to visualise cellular responses to toxic exposures in real-time.
• Omics technologies: Utilise transcriptomics and metabolomics approaches to identify biomarkers of toxicity, elucidate affected pathways, and understand the systemic impact of toxicants.
• Analytical methods: Detect parent compound and metabolites via LC-MS and NMR.

Career prospects: Graduates are well-prepared for diverse roles in academia, industry, and government, including:

• Pharmaceutical and biotechnology companies: Positions as toxicologists, safety scientists, and research scientists involved in drug discovery, safety assessment, and regulatory compliance.
• Environmental and public health agencies: Roles as environmental toxicologists, risk assessors, and policy advisors focusing on chemical safety and environmental health.
• Research institutions and universities: Opportunities as PhD student researchers and educators advancing the field of toxicology through innovative research and teaching.
• Regulatory bodies and non-governmental organisations: Positions as regulatory affairs specialists, consultants, and advocates for chemical safety and public health.

Ideal candidates: This specialisation is designed for students with a background in cellular biology, (bio)-chemistry, pharmacology, or related fields, and a keen interest in understanding the molecular basis of toxicity. Ideal candidates are analytical thinkers with a commitment to scientific research and a passion for improving public health through the study of toxicology.

Programme curriculum highlights: Students in the Molecular Toxicology specialisation gain expertise through a combination of coursework, research projects, and practical training. Key components of the curriculum include:

• Advanced toxicology: An in-depth exploration of toxicological principles, mechanisms of toxicity, and current research topics in molecular toxicology.
• Toxicokinetics and risk assessment: A study of the ADME processes of toxicants, modeling of toxicokinetic data, and methodologies for assessing and managing chemical risks.
• Omics approaches in toxicology: Training in the application of transcriptomics and metabolomics to identify biomarkers and understand toxicological mechanisms.
• Cellular and Molecular Toxicology: The understanding of the major stress-response pathways and methods to study the effect of chemicals/drugs on cells.
• Culturing of advanced human in vitro models: Exploring alternatives to animal models for risk assessment.

Additionally, students undertake a Major Research Project (42-60 ECTS), allowing them to conduct original research in academic, industrial, or governmental settings, and apply their knowledge to real-world toxicological challenges.

Research internship opportunities: Students have access to a wide range of research projects, both within the university and through external collaborations. Examples of internal research internship opportunities include:

1. Mechanistic studies of drug candidates early drug discovery: Investigating how lead compounds in drug discovery potentially can lead to adverse toxic cellular and molecular alterations. Use techniques like transcriptomics, High Content Imaging, RT-PCR, cellular toxicity assays, drug metabolism and metabolomics (HPLC-MS, NMR), Seahorse bioanalyser to detect mitochondria toxicity.
2. Development of in vitro models for toxicity testing: Optimisation and validating of iPSC-derived and primary or cell line-derived cell models to assess the potential toxicity of lead compounds in drug discovery – also known and New Chemical Entities (NCEs) – reducing the need for animal testing.
3. Application of Omics technologies in toxicology: Utilising transcriptomics and metabolomics to identify biomarkers of exposure and effect, and to elucidate mechanisms of toxicity.

External internships may be undertaken at pharmaceutical companies, research institutes, environmental agencies, and regulatory bodies, providing students with exposure to applied toxicology, risk assessment, and regulatory science. These experiences enable students to apply their academic knowledge to practical challenges in drug candidate safety, chemical safety in general, and public health.

By completing the Molecular Toxicology specialisation, graduates will be equipped with the expertise to assess and mitigate the risks associated with chemical exposures, enhancing the (animal-free) approaches to detect safety issues early in drug discovery, focusing on and contributing to the development of safer drugs, and advance the field of toxicology through research and innovation.

Computer-Aided Drug Design: designing next-generation drug molecules

Overview: In the specialisation Computer-Aided Drug Design (CADD), you will learn and apply state-of-the-art molecular modeling and computational chemistry techniques to understand the biomolecular basis of drug action. The obtained insights and knowledge will equip you to build models for bioactive molecular features and protein structures and integrate them with advanced modeling and simulation strategies into workflows for the rational design of next-generation drug compounds, and to aid prevention of unwanted side effects of pharmaceutically active molecules.

Core learning objectives:

• Modeling and simulation methodologies: learn about state-of-the-art methods and models in CADD and their strengths as well as possible limitations
• Design efficiency: make optimal use of advanced methods in a high-computing setting, and work closely together with medicinal chemists to account for synthetic feasibility
• Interdisciplinary and drug context: learn to work with relevant knowledge of biomolecular targets and with data sets from pharmacological and toxicological analyses

Hands-on experience with state-of-the-art technologies: the CADD track incorporates theory of and practical training in advanced modeling and simulation methodologies such as:

• Pharmacophore modeling: incorporate data on bio(in)active compounds into virtual screening campaigns for drug discovery
• Molecular docking and protein-structure prediction: integrate and advance 3D-conformational information into structure-based drug design
• Molecular dynamics simulation and free energy computation: learn state-of-the-art simulation methods and assess the affinity and kinetics of protein interaction and binding
• Data analysis and management: manage and integrate workflows, statistical analysis, and AI tools for advanced analysis of experimental and simulation bioactivity data

Career prospects: 
Graduates are well-prepared for roles as computational (bio)chemists in academic or government institutes, pharmaceutical companies or biotechnology firms, as well as in non-research related jobs in education or policy, or in industries where similar modeling and simulation techniques are used (banking, insurance). Their expertise in molecular modeling and biomolecular simulation positions them well to contribute to drug design, discovery and development. They are also well equipped to continue their career as research scientists in academia.

Ideal candidates: 
This specialisation is designed for students with a strong background in chemistry or in molecular-oriented pharmaceutical sciences, biophysics or bioinformatics, and with a keen interest in understanding and exploring the biomolecular basis for (wanted or unwanted) action of drugs or other biologically-active compounds. A strong commitment to a research-oriented context and a passion for innovation in drug discovery are essential qualities for prospective students.

Program curriculum highlights: 
Students in the CADD specialisation become experts in state-of-the-art molecular modeling and simulation techniques, and become well-rounded team players in a drug research context. Key compulsory courses in this specialisation cover:

• Data Management in Drug Discovery: understand the role of data analysis and management in drug discovery and learn how to work with different types of data, curate them, retrieve information from databases, and apply practical tools for advanced data analysis and basic machine learning to solve real-world problems in drug discovery.
• Computer-Aided Drug Discovery and Virtual Screening: learn, explore and deploy key techniques (pharmacophore and homology modeling, molecular docking, QSAR) in virtual screening campaigns to identify new and better drug molecules.
• Biomolecular Simulation in Drug Discovery: learn and apply molecular dynamics simulation and free-energy computation methodologies with a focus on in-depth studying and understanding of protein-drug interaction.
• (Where applicable) Principles of Drug Targets and Principles of Drug Discovery: learn the fundaments of computer-aided drug design, molecular pharmacology and molecular toxicology necessary for efficiently operating in interdisciplinary research teams
• Research skills and scientific communication: Development of essential research skills, including experimental design, data analysis, and effective communication of scientific findings.

Additionally, students complete a Major Research Project (42-60 ECTS), allowing them to conduct in-depth research in an academic or industrial settings.

Research internship opportunities: Students have access to diverse possibilities for research projects, both within the university and through external collaborations. Examples of internal research internship opportunities include:

1. Drug (or protein) design: build or refine models to understand protein-drug binding and enable design of molecules (or proteins) that enhance target binding (or prevent unwanted binding to off-target proteins)
2. Virtual screening and workflows: based on insights from structure-based models and databases from experiment or literature, establish workflows that include advanced modeling and/or AI tools for virtual screening to repurpose drugs or find new binders  
3. Method and model development: contribute to new free-energy or interaction models (force fields) to advance the field of biomolecular modeling and simulation
4. Drug metabolism: understand and predict metabolism of drug compounds in our body, or other possibly unwanted effects

External internships may be undertaken at universities, pharmaceutical companies or research institutes in the Netherlands or abroad, providing exposure to various and possibly interdisciplinary research settings.

Bioanalytics: unraveling molecular insights in drug discovery

The Bioanalytics specialisation within the Drug Discovery Sciences (DDS) Master’s programme at the Vrije Universiteit Amsterdam offers an in-depth exploration of cutting-edge analytical techniques essential to modern drug discovery and development. This track equips students with the skills to analyse drug candidates, their interactions with protein-based drug targets, and the drug targets themselves, providing a comprehensive understanding of the molecular mechanisms underlying therapeutic interventions. This unique programme emphasises state-of-the-art analytical chemistry, preparing graduates to make significant contributions to life sciences and pharmaceutical research.

Bioanalytics core topics:

• Advanced analytical techniques: students gain proficiency in cutting-edge methods, including mass spectrometry (MS), chromatography, electrophoresis, and nuclear magnetic resonance (NMR) spectroscopy. These tools are key for qualitative and quantitative analysis of drugs and their metabolites in complex biological matrices, and for characterising biological systems at a molecular level.
• Proteomics and metabolomics: -omics approaches are crucial for understanding drug mechanisms, efficacy, and safety profiles. These strategies are used to get a better understanding of how diseases progress at the molecular level in the body and can be used to discover new diagnostic molecules and find novel drug targets. The field of proteomics studies protein structures and functions, thereby placing the human proteome in the broader context of health and disease. Metabolomic approaches allow the analysis of metabolic pathways and how they are deregulated in a disease. In Bioanalytics track of DDS, students discover the advanced approach for performing both proteomic and metabolomic analyses.
• Pharmacokinetics and pharmacodynamics (PK/PD): studying solely a molecule’s structure does not reveal the whole story. In the Bioanalytics track, students learn to analyse the absorption, distribution, metabolism, and excretion (ADME) of drugs, along with their pharmacological effects, to optimise therapeutic outcomes.

These core topics are reflected in three key compulsory courses:

• ADME (Absorption, Distribution, Metabolism, Excretion) (6 ECTS)
• Advanced Bioanalytical Approaches (6 ECTS)
• Biopharmaceuticals & Biopharma Proteomics (6 ECTS)

The Bioanalytics track emphasises hands-on training with advanced instrumentation and methodologies. Students undertake a substantial research project (42-60 ECTS), enabling them to conduct in-depth studies in academic or industrial settings. Key analytical techniques covered in coursework and applied during the internship include:

• Mass Spectrometry Applications: engage with high-resolution MS techniques, including imaging MS and ion mobility MS (IM-MS), to investigate drug-target interactions and protein conformations.
• Separation Techniques: utilise chromatographic separation techniques such as ultra-high-performance liquid chromatography (UHPLC) and high-resolution electrophoresis methods, including capillary electrophoresis (CE), for the separation and analysis of complex biological samples.
• Spectroscopic Methods: apply advanced spectroscopic techniques, such as Raman spectroscopy to study molecular composition or Surface Plasmon Resonance to examine bioaffinity interactions at the molecular level. Work with laser-based infrared (IR) and ultraviolet (UV) spectroscopy within a mass spectrometer to investigate molecular structures and dynamics, supporting the identification of biomarkers and therapeutic targets.

In the Bioanalytics specialisation, the integrated academic skills portfolio plays a vital role in supporting students' research and professional development. Through modules focused on scientific writing, research ethics, and communication, students refine essential skills that enhance their analytical and critical thinking abilities. This portfolio not only strengthens their ability to conduct rigorous research but also prepares them to communicate complex scientific findings effectively, a crucial skill for careers in the life sciences and pharmaceutical industry.

The Bioanalytics specialisation offers students significant freedom in choosing elective courses, allowing them to tailor their studies to specific interests within or beyond analytical chemistry. This flexibility fosters interdisciplinary training, enabling students to gain valuable insights from related fields, such as molecular biology, toxicology, and data science. Such interdisciplinary expertise is highly valued in the pharmaceutical industry, where complex drug discovery challenges require a broad, adaptable skill set and the ability to collaborate across scientific domains.

Career Prospects:
Graduates of the Bioanalytics specialisation are well-prepared for roles in pharmaceutical research and development (R&D), clinical diagnostics, biotechnology, consulting, and regulatory agencies. The comprehensive training in analytical techniques and molecular understanding equips students to contribute to various stages of drug discovery and development, from early discovery to clinical trials and quality control. Beyond the world of pharma, many of our analytical graduates have found their way to life sciences in the broader sense.

Ideal Candidates:
This specialisation is designed for students with a strong interest in analytical sciences and a desire to understand the molecular basis of drug action and disease. A commitment to scientific research and a passion for innovation in drug discovery are essential qualities for prospective students. By integrating theoretical knowledge with practical skills, the Bioanalytics specialisation offers a robust foundation for those aiming to advance the field of drug discovery through analytical excellence.

Research Internship Opportunities:
Students have access to diverse research projects, both within the university and through external collaborations. Internal research internship opportunities within the Bioanalytics specialisation give students access to a wide range of in-depth scientifically oriented projects. These internships, hosted by the division of BioAnalytical Chemistry and related divisions, allow students to gain hands-on experience with advanced analytical techniques, contributing to cutting-edge research in drug discovery and bioanalytics. Some example projects for our internships include:

1. Infrared and Ion Mobility Spectroscopy to investigate neurodegenerative diseases

2. Glycoprotein Mass Spectrometry

3. Venom Bioactivity Profiling & Proteomics

4. Drug Metabolic Fate & Mechanism-of-Action Studies

5. Forensic Analytical Toxicology & Metabolomics

6. Snakebite and Venom Toxins Research

7. Biopharmaceutical Characterisation

8. Molecular Toxicology of Lead Compounds

9. LC-MS bioanalytics for Pharmacokinetics of Drugs and Metabolites in Patient Samples

10. Advanced Analytical Chemistry for Toxicology

Examples of External Internships:
Students may also undertake internships at top institutions, including:

• University Medical Centers: projects on bioanalytical toxicology, pharmacokinetics, and biopharmaceuticals.
• Pharmaceutical Companies: Opportunities to apply analytical techniques in drug discovery & development, quality control, and biomarker discovery.
• Research Institutes: Projects focusing on food and drug safety, analytical technology development relevant to health and society, and quality assurance & safety monitoring institutes.
• International Collaborations: Through programmes like Erasmus, students can pursue internships at universities and research institutions across Europe.