The Master’s specialisation in Drug & Target Discovery offers research-orientated education into advanced systems microscopy technologies and clinically relevant model systems for target and drug screening in combination with cheminformatics for development of novel and safe drug leads. Focus is on targeting hallmarks of cancer.
The two divisions of the Leiden Academic Centre for Drug Research involved in the Master’s specialisation Drug & Target Discovery are:
For medicinal chemistry the ultimate objective concerns the design and synthesis of new compounds, which fulfill a set of properties making them suitable as medicinal agents. Next, the interaction with their targets is studied at atomic resolution. We want to use that understanding for a more rational approach of drug design. We have chosen the most important class of drug targets to work on, the G protein-coupled receptors (GPCRs). Close to half of all medicines work via these targets in our body.
It is impossible to study all receptors, as there are over 800 in the human body. Therefore, we have selected a few to concentrate on: receptors for adenosine (to which caffeine also binds, and that could help find a cure for Parkinson’s disease), for chemokines (neuropathic pain), for nicotinic acid (cardiovascular diseases), for endocannabinoids (obesity), for glutamate (schizophrenia), for the gonadotropine-releasing hormone (involved in breast and prostate cancers) and even receptors for which we have not found the ligands yet (adhesion GPCRs). Next to this, we are also interested in how drugs interact with other proteins, and thus we also have an ongoing project on ion channels, which play an important role in drug safety.
We pursue a ‘chemical biology’ approach, in which we combine synthetic chemistry, new developments in the world of informatics and computer science (bioinformatics, cheminformatics), and both biochemistry/molecular biology and pharmacology. Hence, at the Division of Medicinal Chemistry we have all ingredients to come up with ideas for new drugs, make them, and establish how they work.
The unraveling of the human genome has allowed the systematic evaluation of perturbed expression and/or mutations of genes in relation to disease development and/or progression. Global transcriptomics and proteomics analysis has allowed the identification of gene and protein networks that are perturbed in disease. Subsequently, systematic genome-wide gene function analysis has become possible though RNA interference (RNAi).
At the Division of Toxicology such datasets are integrated to understand cancer cell migration and drug resistance as well as drug toxicity. We also couple these analyses to high throughput, high content image based RNAi screens using fluorescent reporters. Such a “systems microscopy” approach to analyze dynamic cell biological processes opens exciting new opportunities for identification of novel drug targets.
On the one hand, mechanisms of drug toxicity identified in this manner are used to develop better in vitro tools for human drug safety predictions. On the other hand, signaling networks underlying drug resistance or motility of cancer cells that we identify are further explored in advanced 3D culture systems and in vivo models. The ultimate goal here is to develop targets for more effective cancer therapy that can be translated to clinical development.