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Structural characterization and inhibition of the interaction between ch-TOG and TACC3

In this paper we describe the structure of the interaction between TACC3 and ch-TOG. A single helix from ch-TOG, normally bound to two hairpins, pops out and binds to the coiled-coil of TACC3. We then isolated Affimers (non-antibody binders) that inhibit this interaction in vitro. Moving into cells, we could express the Affimers to inhibit the ch-TOG–TACC3 interaction and found a new function for these two proteins in stabilizing the pericentriolar material.
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Mon 10 Jun 2024, 09:05 | Tags: BMS BMS_newpub

Non-disruptive inducible labeling of ER-membrane contact sites using the Lamin B Receptor

Laura Downie has invented a new way of labelling ER-Membrane Contact Sites in live cells on-demand. It uses the Lamin B Receptor so we called it “LaBeRling”. Unlike other methods, LaBeRling doesn’t distort existing contacts. It can label many different contacts between ER and other organelles (plasma membrane, mitochondria, lysosomes, endosomes, lipid droplets). Here, Laura uses LaBeRling to look at ER-Golgi contact sites in mitosis for the first time.
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Mon 10 Jun 2024, 09:03 | Tags: BMS BMS_newpub

Bariatric surgery for spontaneous ovulation in women living with polycystic ovary syndrome: the BAMBINI multicentre, open-label, randomised controlled trial

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility. Obesity exacerbates the reproductive complications of PCOS; however, the management of obesity in women with PCOS remains a large unmet clinical need. Observational studies have indicated that bariatric surgery could improve the rates of ovulatory cycles and prospects of fertility; however, the efficacy of surgery on ovulation rates has not yet been compared with behavioural modifications and medical therapy in a randomised trial. The aim of this study was to compare the safety and efficacy of bariatric surgery versus medical care on ovulation rates in women with PCOS, obesity, and oligomenorrhoea or amenorrhoea.
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Tue 28 May 2024, 10:24 | Tags: BMS BMS_newpub

Interdisciplinary Biomedical Research Building awarded RIBA West Midlands Building of the Year

Our Interdisciplinary Biomedical Research Building, which we share with the School of Life Sciences, has been awarded the West Midlands Building of the Year award from the Royal Institute of British Architects.

Mon 13 May 2024, 11:37 | Tags: news BMS

Global spread of Salmonella enterica due to centralised industrialisation of pig farming

In a collaboration between Soochow (China), Institut Pasteur (Shanghai), CDC (China), Liverpool, Georgia (US), and Warwick we investigated the host-specificity of S. enterica based on 362,931 publically accessible genomes in EnteroBase (a database of sequenced enteric bacteria genomes hosted and developed at Warwick). We detected the presence of nine populations that are enriched in pigs and observed frequent intercontinental transmission of genetically almost identical strains in these pig-enriched populations, which cannot be explained solely by natural causes. Therefore, we focused on one population enriched in pigs, serovar Choleraesuis, reconstructing the historical fluctuations in this population, accumulation of antimicrobial-resistant genes, and international transmissions. We revealed a 2-stage expansion in the population of this serovar, the first associated with the development of intensive pig farming in the early 20th century and the second due to the increased frequency of antimicrobial resistance after the 1960s. Additionally, we found that Europe and the USA contributed the most to international transmissions of this serovar.
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Mon 13 May 2024, 09:26 | Tags: BMS BMS_newpub

Professor Robert Cross awarded Biochemical Society Award for Sustained Excellence 2025

Professor Robert Cross, Warwick Medical School has been awarded the Biochemical Society Award for Sustained Excellence 2025.

The work and contribution of fifteen eminent bioscientists, outstanding educators and exceptional early career researchers has been acknowledged in the annual Biochemical Society Awards following a record year of nominations - Find out more and read the full article here

Thu 04 Apr 2024, 10:56 | Tags: news BMS

Long-range formation of the Bicoid gradient requires multiple dynamic modes that spatially vary across the embryo

Morphogen gradients provide essential positional information to gene networks through their spatially heterogeneous distribution, yet how they form is still hotly contested, with multiple models proposed for different systems. Here, we focus on the transcription factor Bicoid (Bcd), a morphogen that forms an exponential gradient across the anterior-posterior (AP) axis of the early Drosophila embryo. Using fluorescence correlation spectroscopy we find there are spatial differences in Bcd diffusivity along the AP axis, with Bcd diffusing more rapidly in the posterior. We establish that such spatially varying differences in Bcd dynamics are sufficient to explain how Bcd can have a steep exponential gradient in the anterior half of the embryo and yet still have an observable fraction of Bcd near the posterior pole. In the nucleus, we demonstrate that Bcd dynamics are impacted by binding to DNA. Addition of the Bcd homeodomain to eGFP::NLS qualitatively replicates the Bcd concentration profile, suggesting this domain regulates Bcd dynamics. Our results reveal how a long-range gradient can form while retaining a steep profile through much of its range. Read the paper here.

Tue 12 Mar 2024, 08:45 | Tags: BMS BMS_newpub

TimeTeller: A tool to probe the circadian clock as a multigene dynamical system

More and more evidence suggest that circadian clock disruption or misalignment is a feature of many diverse chronic diseases including metabolic syndrome, depression but also a number of cancers. For the latter, recent mechanistic studies in cancer models have established an understanding of how the circadian clock influences onset, progression and therapeutic outcomes. Moreover, it has been proposed that tumours might have disrupted circadian oscillators. In patients, however, this is more difficult to establish as usually only single samples, e.g., tumour biopsies, are available. Therefore, novel tools to measure the functional state of the molecular circadian clock are needed.

Here, we introduce TimeTeller, a machine learning tool that analyses the clock as a system and aims to estimate circadian clock function from a single sample’s transcriptome by modelling the multi-dimensional state of the clock. We demonstrate TimeTeller’s utility for analysing experimental in vitro and in vivo, as well as healthy human and patient samples from various platforms (microarray, RNA-Seq and NanoString) and highlight TimeTeller’s potential relevance for advancing circadian medicine. The project is an inter-disciplinary collaboration including significant work by Warwick’s MRCDTP students Laura Usselmann and Vadim Vasilyev and is setting the stage for further applications of TimeTeller in experimental models and human breast tumours.
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Tue 05 Mar 2024, 09:08 | Tags: BMS BMS_newpub

Personalized Chronomodulated 5-Fluorouracil Treatment: A Physiologically Based Pharmacokinetic Precision Dosing Approach for Optimizing Cancer Therapy

This work is based on the discovery of diurnal variations impacting cancer therapy. Especially, use of chronomodulated treatment with 5-fluorouracil (5-FU) has gained significance. Studies indicate high inter-individual variability in diurnal variations in dihydropyrimidine dehydrogenase (DPD) activity – a key enzyme for 5-FU metabolism. However, the influence of individual chronotypes on chronomodulated therapy was unclear but is needed to optimize precision dosing of chronomodulated 5‑FU. Lead by the Thorsten Lehr's PKPD group at the University of Saarland, this collaborative paper is taking a treasure trove of patient 5-FU PK data amalgamated with DPD enzyme activity data from health people to establish a novel PKPD model of 5-FU that captures the extent of diurnal variations in DPD activity and can help investigate individualized chronomodulated 5-FU therapy through testing alternative personalized dosing strategies. Read the paper here.

Thu 25 Jan 2024, 08:50 | Tags: BMS BMS_newpub

Dr Meera Unnikrishnan awarded over £2 million for research into C. difficile infection

Associate Professor Meera Unnikrishnan from the Division of Biomedical Sciences has been awarded a Wellcome Discovery Award from the Wellcome Trust to the value of £2,225,509. Her project, ‘Dissecting Clostridioides difficile-host-commensal interactions at the gut interface’, will take place over eight years.

Wed 06 Dec 2023, 11:54 | Tags: news BMS

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