Warwick MB ChB finalist Thomas Dale MacLaine recently attended a garden party at Buckingham Palace in recognition of his services to Higher Education. We caught up with him to find out more about the experience and why he was recognised.
Our 2022 MB ChB Prizegiving Evening took place on 11 May, celebrating the fantastic work and achievements of our medical students over the last year and excellence amongst our staff.
Characterisation of the Ubiquitin-ESCRT pathway in Asgard archaea sheds new light on origins of membrane trafficking in eukaryotes
This work answers the mystery surrounding when in evolution did a key class of membrane remodelling factors arise. The collaborative team comprising Balasubramanian (Warwick), Baum (Cambridge), Lowe (Cambridge), Robinson (Lancaster), and Ettema (Wageningen, Netherlands) worked on proteins encoded by Heimdall archaea, thought to be most related to eukaryotes. They found that, contrary to existing dogma, a complex eukaryote-like ESCRT family of membrane remodelling factors were present in archaea and are therefore not eukaryotic inventions. Warwick post-doctoral fellow and first author Hatano “reconstituted” key steps of the process using purified components helping arrive at the conclusions.
Read the paper hereLink opens in a new window.
This 3.5 year PhD studentship provides a unique opportunity for a promising social or health science researcher to undertake research aimed at influencing the future of palliative care services. The student will investigate the relationship between wider ideas of society and healthcare as complex and how palliative care understands itself as addressing people’s ‘complex needs’.
Many congratulations to Professor Harbinder Sandhu, who has been shortlisted as a finalist for the 2022 Asian Women of Achievement AwardsLink opens in a new window in the science category. This is to represent the work she is doing in her research here at Warwick and clinically.
New research at the University of Warwick will investigate whether many of the physical and psychological effects of ageing are already determined for us by the time we are born thanks to new funding of over 2 million euros.
Research from the University of Warwick sheds new light on a key cause of cancer formation during cell division (or mitosis), and points towards potential solutions for preventing it from occurring.
Development is more than just growth: Understanding the mechanics of organ shrinkage during embryo formation
When we think about embryo growth, we often focus on tissue growth. However, this is not always the case: for example, the nervous system actually shrinks during parts of development. How do tissues condense in size while maintaining mechanical integrity? In recent work from the Saunders lab, with Spanish collaborators Enrique Martin-Blanco and Jose Munoz, they show that the Drosophila nervous system condenses through alternating waves of contraction from the anterior and posterior ends of the embryo. Further, they use the power of Drosophila genetics to reveal that the glial cells provide an essential mechanical support, effectively acting like a compression sock during condensation. This work opens up new avenues to study the mechanobiology of tissues that shrink – such tissues display behaviour very much distinct from growing tissues. Read the paper here.
Life is the (mito)pits
The formation of a clathrin-coated vesicle is a major membrane remodeling process that is crucial for membrane traffic in cells. Besides clathrin, these vesicles contain at least 100 different proteins although it is unclear how many are essential for the formation of the vesicle. Here, we show that intracellular clathrin-coated formation can be induced in living cells using minimal machinery and that it can be achieved on various membranes, including the mitochondrial outer membrane. Chemical heterodimerization was used to inducibly attach a clathrin-binding fragment "hook" to an "anchor" protein targeted to a specific membrane. Endogenous clathrin assembled to form coated pits on the mitochondria, termed MitoPits, within seconds of induction. MitoPits are double-membraned invaginations that form preferentially on high curvature regions of the mitochondrion. Upon induction, all stages of CCV formation - initiation, invagination, and even fission - were faithfully reconstituted. We found no evidence for the functional involvement of accessory proteins in this process. In addition, fission of MitoPit-derived vesicles was independent of known scission factors including dynamins and dynamin-related protein 1 (Drp1), suggesting that the clathrin cage generates sufficient force to bud intracellular vesicles. Our results suggest that, following its recruitment, clathrin alone is sufficient for intracellular clathrin-coated vesicle formation.
Read more hereLink opens in a new window.
Understanding how to stop ice growth with amino acids
The GibsonGroup, working with the Sosso Group in chemistry have demonstrated that simple amino acids can slow the recrystallisation of ice. Ice recrystallisation inhibition (IRI) is normally associated with ice binding proteins, but the team show that amino acids can also achieve this. Using a combination of experiments and modelling the importance of the structure of the amino acid is explored, and the relative role of ice binding investigated.
Read the paper here.
Detecting SARS-COV-2 Using Plasmonic Nanoparticles
The GibsonGroup, working with colleagues at UHCW, have demonstrated the detection of SARS-COV-2 virus using liquid samples. The team, in 2020, discovered that SARS-COV-2 spike protein could bind sialic acids (specialised sugars) and developed this for lateral-flow detection. In this present work, the team show a solution-phase assay which can be conducted in multiwell plates and is hence suitable for automation. The key design of this was rod-shaped gold nanoparticles, with a synthetic polymer tether connecting the sugars.
Read the paper here
A project to improve the efficiency of our medicines using tiny particles at the University of Warwick has received funding to take it a step closer towards commercialisation.
Getting the embryo into position
During development, many organisms initially undergo multiple rounds of nuclei division before cellularisation occurs. Such systems are known as syncytia. Other processes such as muscle formation – which have multiple nuclei in a single cell – are similar.
In syncytia, nuclei distribute in a regular pattern. Yet, how does this occur? Answering this question is important for understanding how life developments and muscles form. In recent work from the Saunders lab, in collaboration with the Telley lab at the Gulbenkian Institute in Portugal, they used quantitative measurements to unravel how the nuclei regularly position in the fruit fly syncytium. They took advantage of explants – whereby material is removed from the egg and imaged – to reveal that are repulsive interactions between microtubules (rod like structures) in the syncytia. They used modelling and experimental tests to show that these repulsive interactions drive the ordering of the nuclei.
Read the paper here.
New Induction Training for Data Protection & Information Security launches 31 January 2022
Following the summer '21 launch of our new Annual Refresher course on Data Protection & Information Security, we have now completed production of a single new Induction course. It will be ready for launch and use by all new employees from 31 January 2022 as part of their mandatory new starter training.
Cell-Type-Specific Circadian Bioluminescence Rhythms in Dbp Reporter Mice
In collaboration with groups at UMass Med School, Smith College and Morehouse University, we have developed a reporter mouse generated by modification of a widely expressed and highly rhythmic gene encoding D-site albumin promoter binding protein (Dbp). In this line of mice, firefly luciferase is expressed from the Dbp locus in a Cre recombinase-dependent manner, allowing assessment of bioluminescence rhythms in specific cellular populations. Our studies reveal cell-type-specific characteristics of rhythms among neuronal populations and liver cells. Our model allowed assessment of the rate of recovery from circadian misalignment once animals were provided with food ad libitum. These studies confirm the previously demonstrated circadian misalignment following environmental perturbations and reveal the utility of this model for minimally invasive, longitudinal monitoring of rhythmicity from specific mouse tissues.
Read the paper here.
Lighting Up Tumour Treatments
The Perrier Lab have just published a new study in Angewandte Chemie which shows how polymeric nanotubes can be designed to switch their fluorescence on as they deliver a commercial anticancer drug (doxorubicin), thereby permitting the in-situ visualization of drug release. By this method, we can both treat a cancer tumour and show where the tumour is located. These theranostic systems (from therapeutic and diagnostic) form a new approach to drug delivery.
Read the paper here.
WBS/UAPC PhD studentship on “Health, climate change and innovation- Supporting the sustainability transition in the health care sector”.
This is a WBS/UAPC PhD studentship on “Health, climate change and innovation- Supporting the sustainability transition in the health care sector”. The research will develop a programme theory with which to propose and evaluate specific interventions designed to support the sustainability transition in the primary health care sector.
Extremely concerning levels of psychological distress are reported in results from a longitudinal study of the UK nursing and midwifery workforce during COVID-19 led by Warwick Medical School.
GibsonGroup COVID-19 work featured in Medical School Council Report
The Medical Schools Council has released its report into how university research contributed during the COVID-19 pandemic. Work undertaken by the GibsonGroup is featured in this report.
Kinetochore life histories reveal an Aurora-B-dependent error correction mechanism in anaphase
Chromosome mis-segregation during mitosis leads to aneuploidy, which is a hallmark of cancer and linked to cancer genome evolution. Errors can manifest as ‘‘lagging chromosomes’’ in anaphase, although their mechanistic origins and likelihood of correction are incompletely understood. Here, we combine lattice light-sheet microscopy, endogenous protein labeling, and computational analysis to define the life history of >104 kinetochores. By defining the ‘‘laziness’’ of kinetochores in anaphase, we reveal that chromosomes are at a considerable risk of mis-segregation. We show that the majority of lazy kinetochores are corrected rapidly in anaphase by Aurora B; if uncorrected, they result in a higher rate of micronuclei formation. Quantitative analyses of the kinetochore life histories reveal a dynamic signature of metaphase kinetochore oscillations that forecasts their anaphase fate. We propose that in diploid human cells chromosome segregation is fundamentally error prone, with an additional layer of anaphase error correction required for stable karyotype propagation. Read the paper here
Cryopreservation of Phage
The GibsonGroup, working with the Sagona group in SLS and Cytivia (who host Prof Gibson as a Royal Society Industry fellow) have investigated how polymers can be used to cryopreserve bacteriophages. Methods to freeze cells have attracted huge interest of late, for application in cell based therapies and biotechnology. However, virus storage is less explored. The team showed that a simple commodity polymer could (surprisingly) protect phage and offers a new approach for banking, or even storing cocktails of phages for future use in therapy or diagnostics.
Read the paper here
The General Medical Council (GMC) which oversees the training of doctors in the UK is set to approve a new course at Chester Medical School, developed with the support of the University of Warwick/
An Entirely Glycan-Based Lateral flow device
The GibsonGroup and their Industrial partners Iceni Diagnostics have been collaborating on new tools for Lateral Flow Diagnostics(LFDs). In particular, on replacing antibodies as the recognition units with glycans (sugars). Here the team show the first example of a complete LFD which uses glycans as both the mobile and stationary phase, providing complete proof-of-concept that a lateral flow diagnostic can be achieved without antibodies. This is demonstrated for the sensitive detection of lectins and could be applied to a range of biological targets, spanning toxins, viruses and more.
Read the paper here
Removing the need for proteins in lateral flow diagnostics
The GibsonGroup with their industry partner Iceni Diagnostics have demonstrated a new approach to make ’test lines’ in lateral flow diagnostics. Current methods to make a test line involve immobilising antibodies, or using high molecular weight proteins with chemical modifications to display binding ligands. In this work, the team showed that a synthetic polymer can be used instead, which could dramatically simply the process of making a new test line, and using ’small molecule ligands’ as the targets, shown here with a glycan and biotin.
Read the paper here