Hess Lab | Metal- Heterobifunctional Scaffolds to Capture Proteins

A 2026 Crick PhD project with Jeannine Hess.

Bioinorganic chemistry is an exciting and rapidly growing field with the potential to address major biological challenges through the use of metal‑based compounds. Metal complexes have long been central to medicine and include some of the most successful anticancer drugs developed to date. Metal centres can endow organic scaffolds with unique properties, such as enhanced molecular shape diversity, or undergo ligand exchange reactions that enable strong and selective interactions with biomolecular targets [1–4].

Our mission is to develop innovative technologies for the rational design of metal‑based molecules as new chemical modalities in discovery science.

Building on our recently developed LAMP-D technology (Light‑Activated Metal‑dependent Protein Degradation), this PhD project will design and synthesise metal complexes decorated with diverse organic directing and targeting units [5]. These compounds will be explored as novel chemical probes and therapeutic candidates to tackle challenging and “undruggable” protein targets. You will investigate their biological activity, uptake, selectivity, and mechanism of action, while probing distinctive metal‑specific features such as ligand exchange, redox reactivity, and catalysis.

We are seeking a highly motivated PhD student eager to develop new concepts at the interface of chemistry and biology. You will employ state‑of‑the‑art synthetic and analytical methods to generate rationally designed compounds and apply biophysical and biochemical techniques (DSF, ligand‑based NMR, ITC, in vitro enzymatic assays, protein expression) to evaluate their mechanism of action.

By joining our group, you will contribute to pioneering science and help foster an open, collaborative lab culture that values creativity and interdisciplinary teamwork. Together, we aim to deliver transformative chemical tools and therapeutic strategies to combat drug‑resistant bacteria and advance fundamental biological discovery.

• You are motivated to work at the forefront of bioinorganic chemistry and to develop new approaches and strategies to design and generate metal complexes with novel 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

• Soldevila‑Barreda, J.J. and Metzler‑Nolte, N. (2019)
  Intracellular catalysis with selected metal complexes and metallic nanoparticles:
  Advances toward the development of catalytic metallodrugs. Chemical Reviews 119
  : 829-869. Pub Med abstract
• Waters, J.E., Stevens‑Cullinane, L., Siebenmann, L. and Hess, J. (2023)
  Recent advances in the development of metal complexes as antibacterial agents with metal‑specific modes of action. Current Opinion in Microbiology 75
  : 102347. Pub Med abstract
• Rees, T.W., Ho, P.Y. and Hess, J. (2023)
  Recent advances in metal complexes for antimicrobial photodynamic therapy. Chem Bio Chem  
  24
  : e. Pub Med abstract
• Boros,
  
  E., Dyson, P.J. and Gasser, G. (2020)
  Classification of Metal‑based Drugs According to Their Mechanisms of Action. Chem 6: 41-60. Pub Med abstract