Christian Diercks studied chemistry at the University of Heidelberg and carried out undergraduate research in the group of Prof. Jean-Pierre Sauvage at the University of Strasbourg (France), as well as at Northwestern University (USA) under the guidance of Sir James Fraser Stoddart. He obtained his Ph.D. from UC Berkeley under the mentorship of Prof. Omar M. Yaghi in 2018 for his work on covalent organic frameworks. Currently,hei sapostdoctoral researcher in the group of Prof. Peter G. Schultz at the Scripps Research Institute, working on adding new chemistries to the processes of the central dogma of molecular biology.

The proteasome is a vital cellular machine that maintains protein homeostasis, which is of particular importance in multiple myeloma and possibly other cancers. Targeting proteasome 20S peptidase activity with bortezomib and carfilzomib has been widely used to treat myeloma. However, not all patients respond, and those that do eventually suffer relapse. Therefore, there is an urgent and unmet need to develop novel drugs that target proteostasis through different mechanisms. We identified quinoline-8-thiol (8TQ) as a first-in-class inhibitor of the proteasome 19S subunit Rpn11. A derivative of 8TQ, capzimin, shows >5-fold selectivity for Rpn11 over the related JAMM proteases and >2 logs less activity towards metalloenzymes. Capzimin stabilized proteasome substrates, induced an unfolded protein response, and blocked proliferation of cancer cells, including those resistant to bortezomib. Proteomic analysis revealed that capzimin stabilized a subset of polyubiquitinated substrates. Identification of capzimin offers an alternative path to develop proteasome inhibitors for cancer therapy.

Metal-organic frameworks (MOFs) are microporous materials with huge potential for chemical processes, including retention or separation of guest molecules. Structural collapse at high-pressure, and transitions to liquid states at high temperature, have recently been observed in this family. Here, we show that the effect of simultaneous high pressure and temperature application on ZIF-62 and ZIF-4 results in complex behaviour, with distinct high-and low-density amorphous phases occurring over different regions of the pressure-temperature phase diagram. In-situ powder X-ray diffraction, Raman spectroscopy and optical microscopy reveal that the stability of the liquid MOF-state expands significantly towards lower temperatures at intermediate, industrially achievable pressures. Furthermore, the MOF-glass formed by melt quenching the high temperature liquid is shown to demonstrate permanent, accessible porosity. Our results thus imply a novel route to the synthesis of functional MOF glasses at low temperatures, avoiding decomposition upon heating at ambient pressure.

Posttranscriptional regulation of genes of mammalian iron metabolism is mediated by the interaction of iron regulatory proteins (IRPs) with RNA stem-loop sequence elements known as iron-responsive elements (IREs)