Metal-based Heterobifunctional Scaffolds to Capture Challenging Proteins

A 2025 Crick PhD project with Jeannine Hess. 

Bioinorganic chemistry is an exciting and rapidly growing research area with the potential to address biological challenges through the use of metal-based compounds. Metal-based complexes have long been used in medicine and are among the most successful anti-cancer drugs developed to date. Metal centres can bring new features to organic scaffolds such as increasing the shape diversity or can undergo ligand exchange reactions resulting in strong binding to biomolecular targets. [1,2,3,4]

This project will develop and apply target-based and structure-guided approaches [5] to design metal complexes that are decorated with different organic directing and targeting units. We will then study the biological activity of these new metal-based modalities, their uptake, selectivity, as well as their mechanism of action. 

We are looking for a highly motivated PhD student to design and apply new concepts to the field of bioinorganic chemistry and develop inorganic probes that target challenging and/or undruggable proteins. You will rely extensively on state-of-the-art chemical synthesis and analytical chemistry to generate new, rationally designed compounds with biological activity. You will also use and develop a variety of approaches to guide the design and optimisation of the compounds and to test their biological activity. These include protein expression, a wide range of biophysical techniques such as differential scanning fluorimetry (DSF), ligand-based NMR spectroscopy, isothermal titration calorimetry (ITC), and in-vitro enzymatic assays. 

Importantly, you will also help building and maintaining an open and collaborative lab atmosphere that nurtures scientific creativity and productivity, complementing our team on the mission towards new therapeutics against drug-resistant bacteria.

Candidate background

• You are motivated to work at the forefront of bioinorganic chemistry and to develop new approaches and strategies to generate inorganic or organometallic compounds with interesting biological activity.
• You have practical experience in organic synthesis, organometallic chemistry, medicinal chemistry, chemical biology, bioinorganic chemistry or any related field.
• You are creative, have excellent communication skills, are enthusiastic about working collaboratively in a multidisciplinary research area and are interested in learning and adopting relevant techniques to achieve the research goals.