Daum Group Welcome to our group! We employ the method of electron cryo-microscopy (cryoEM) to determine the structure and function of molecular machines and assemblies, which form the very fabric of life. Our research will provide important new insights into the inner workings of cells and also inform new ways to re-engineer biomolecules for novel applications in nanotechnology and drug delivery. Our Research THE STRUCTURE OF MICROBIAL CELL WALLS Many bacteria and most archaea are enveloped in S-layers, protective lattices of proteins. These S-layers define both the cell’s shape and periplasmic space and play essential roles in cell division, adhesion, biofilm formation, protection against harsh environments and phages and comprise important virulence factors in pathogenic bacteria. We investigate the structure S-layers in order to gain a deeper understanding into their function and to explore how these fascinating protein lattices can be engineered into novel materials in nanotechnology and drug delivery. THE STRUCTURE AND FUNCTION FLAGELLA AND PILI Microorganisms use a variety of filaments that extend up to several micrometers from the cell surface. These filaments have a wide spectrum of functions essential to microbial life: They enable cells to move, adhere to surfaces, and interact with each other and their environment. These filaments are controlled by molecular machines that are anchored to the cell membrane and drive their assembly and motion. Our lab uses cryoEM to study the structure and function of these filaments and the molecular machines that control them. Our work will shed new light on microbial biology and has important implications for drug development and synthetic biology. STUDYING EUKARYOTIC INTRACELLULAR PARASITES Using electron cryo-tomography, we investigate how tiny eukaryotic parasites called microsporidia infect animal and human cells. Our work will provide new insights into how to combat infectious diseases at the molecular level. INVESTIGATING RIBOSOME HIBERNATION IN EUKARYOTES Dormancy is an essential developmental process in many organisms, including bacteria, plants, fungi, and animals. We study the cellular process of dormancy in eukaryotes and the role that ribosomes play within it. Our work will shed new light on how ribosomes are switched off as cells transition into dormancy and how ribosomes are reactivated again when the cells “reawaken” from dormancy. FULLY FUNDED PHD STUDENTSHIP AVAILABLE! The Daum Lab is recruiting a motivated PhD candidate: Thesis Title: Unlocking the molecular mechanisms governing stem cell dormancy Project description: Cells in many organisms can enter a deep sleep mode called dormancy. This crucial biological process enables cells to endure harsh conditions by reducing their metabolism to a minimum, conserving energy during periods of nutrient scarcity or environmental stress. In eukaryotes, dormancy is crucial to developmental stages, for example in plant seeds, fungal spores, and mammalian egg cells, and is a typical feature of stem cells. Dormancy is also a key factor in cancer because it enables some cancerous cells to persist during chemotherapy and cause disease relapse years later. One of the most energy-demanding processes is protein biosynthesis, costing actively metabolising cells up to 40% of their chemical energy currency ATP. Upon transitioning into dormancy, cells reduce this energy cost as much as possible, by shifting their protein production factories, the ribosomes, into a “hibernation” mode. To keep the dormant cells alive, some ribosomes must remain active to produce essential proteins. Despite the importance of this process for dormancy across the tree of life, its molecular mechanisms are poorly understood. In this interdisciplinary PhD project, you will investigate the mechanism of ribosome hibernation in dormant embryonic mouse stem cells from the cellular to the molecular level. By combining cutting-edge RNA-sequencing, proteomics and confocal microscopy, you will quantify the reduction of ribosome activity in dormant cells, where in those cells residual ribosome activity is maintained, and which essential proteins are still produced. By state-of-the-art cryo-electron tomography, you will solve the structure of the hibernating ribosomes in dormant cells, determine the factors that keep them switched off and visualise the conformational changes that occur when the ribosomes transition into hibernation. Using modern genetic modification techniques (CRISPR), you will then overexpress or knock out the hibernation factors identified and examine, if this can be used induce or abolish dormancy in stem cells. This project is the ideal opportunity to work in a truly interdisciplinary, diverse, and inclusive research team. You will work at the interface of three diverse research groups (Daum and Smith) housed at the Living Systems Institute at the University of Exeter. You will collaborate with experts across fields, blending biology, imaging, structural biology and bioinformatics to decipher living systems. You will acquire expertise in cutting-edge research techniques, which will place you at the forefront of research into life’s most fundamental processes. Your work will significantly impact our understanding of stem cell dormancy, embryo development, and potentially inspire new cancer treatments. If you are interested, please get in touch via email: b.daum2@exeter.ac.uk. To find out more about the Daum Group check out our website!