With over 80% of our research outputs rated as 'internationally excellent' or 'world-leading', the School of Life Sciences continues to drive innovative research that pushes the boundaries of our understanding across the biological sciences.
Here are some of our recent highlights.
Moore, Sam, Hill, Edward M., Tildesley, Michael J., Dyson, Louise and Keeling, Matt J. (2021) Vaccination and non-pharmaceutical interventions for COVID-19: a mathematical modelling study. Lancet Infectious Diseases.
By combining models of vaccination with the methods of forwards projection, we considered the interaction between the relaxation of non-pharamaceutical interventions (NPIs) and the protection offered by the vaccine. This paper set the tone for unlocking the UK in 2021: Our modelled scenarios highlighted the risks associated with early or rapid relaxation of NPIs, stressing the need for slow release of control measures if large-scale waves of infection are to be avoided. We conclude that while the vaccines against SARS-CoV-2 offer a potential exit strategy for the pandemic, success is highly contingent on the precise vaccine properties and population uptake.
Shanshan Zhou, Hussain Bhukya, Nicolas Malet, Peter J. Harrison, Dean Rea, Matthew J. Belousoff, Hariprasad Venugopal, Paulina K. Sydor, Kathryn M. Styles, Lijiang Song, Max J. Cryle, Lona M. Alkhalaf, Vilmos Fülöp, Gregory L. Challis and Christophe Corre. (2021) Molecular basis for control of antibiotic production by a bacterial hormone. Nature.
Actinobacteria produce numerous antibiotics and other specialized metabolites that have important applications in medicine and agriculture1. Diffusible hormones frequently control the production of such metabolites by binding TetR family transcriptional repressors (TFTRs), but the molecular basis for this remains unclear2. The production of methylenomycin antibiotics in Streptomyces coelicolor A3(2) is initiated by the binding of 2-alkyl-4-hydroxymethylfuran-3-carboxylic acid (AHFCA) hormones to the TFTR MmfR3. Here we report the X-ray crystal structure of an MmfR–AHFCA complex, establishing the structural basis for hormone recognition. We also elucidate the mechanism for DNA release upon hormone binding through the single-particle cryo-electron microscopy structure of an MmfR–operator complex. DNA binding and release assays with MmfR mutants and synthetic AHFCA analogues define the role of individual amino acid residues and hormone functional groups in ligand recognition and DNA release. These findings will facilitate the exploitation of actinobacterial hormones and their associated TFTRs in synthetic biology and in the discovery of new antibiotics.
Sally Hilton, Emma Picot, Susanne Schreiter, David Bass, Keith Norman, Anna E. Oliver, Jonathan D. Moore, Tim H. Mauchline, Peter R. Mills, Graham R. Teakle, Ian M. Clark, Penny R. Hirsch, Christopher J. van der Gast and Gary D. Bending. (2021) Identification of microbial signatures linked to oilseed rape yield decline at the landscape scale. Microbiome.
The plant microbiome plays a vital role in determining host health and productivity. However, we lack real-world comparative understanding of the factors which shape assembly of its diverse biota, and crucially relationships between microbiota composition and plant health. Here we investigated landscape scale rhizosphere microbial assembly processes in oilseed rape (OSR), the UK’s third most cultivated crop by area and the world's third largest source of vegetable oil, which suffers from yield decline associated with the frequency it is grown in rotations. We show that at the landscape scale, OSR crop yield is governed by interplay between complex communities of both pathogens and beneficial biota which is modulated by rotation frequency. Our comprehensive study has identified signatures of dysbiosis within the OSR microbiome, grown in real-world agricultural systems, which could be used in strategies to promote crop yield.
van de Wiel J, Meigh L, Bhandare A, Cook J, Nijjar S, Huckstepp RT & Dale N. (2020) Connexin26 mediates CO2-dependent regulation of breathing via glial cells of the medulla oblongata. Communications Biology.
Breathing is highly sensitive to the PCO2 of arterial blood. Although CO2 is detected via the proxy of pH, CO2 acting directly via Cx26 may also contribute to the regulation of breathing. Here we exploit our knowledge of the structural motif of CO2-binding to Cx26 to devise a dominant negative subunit (Cx26DN) that removes the CO2-sensitivity from endogenously expressed wild type Cx26. Expression of Cx26DN in glial cells of a circumscribed region of the mouse medulla - the caudal parapyramidal area – reduced the adaptive change in tidal volume and minute ventilation by approximately 30% at 6% inspired CO2. As central chemosensors mediate about 70% of the total response to hypercapnia, CO2-sensing via Cx26 in the caudal parapyramidal area contributed about 45% of the centrally-mediated ventilatory response to CO2. Our data unequivocally link the direct sensing of CO2 to the chemosensory control of breathing and demonstrates that CO2-binding to Cx26 is a key transduction step in this fundamental process.
Branko Rihtman, Richard J. Puxty, Alexia Hapeshi, Yan-Jiun Lee, Yuanchao Zhan, Slawomir Michniewski, Nicholas R. Waterfield, Feng Chen, Peter Weigele, Andrew D. Millard,David J. Scanlan, and Yin Chen. (2021) A new family of globally distributed lytic roseophages with unusual deoxythymidine to deoxyuridine substitution. Current Biology.
Marine bacterial viruses (bacteriophages) are abundant biological entities that are vital for shaping microbial diversity, impacting marine ecosystem function, and driving host evolution. The marine roseobacter clade (MRC) is a ubiquitous group of heterotrophic bacteria that are important in the elemental cycling of various nitrogen, sulfur, carbon, and phosphorus compounds. Bacteriophages infecting MRC (roseophages) have thus attracted much attention and more than 30 roseophages have been isolated the majority of which belong to the N4-like group (Podoviridae family) or the Chi-like group (Siphoviridae family), although ssDNA-containing roseophages are also known. In our attempts to isolate lytic roseophages, we obtained two new phages (DSS3_VP1 and DSS3_PM1) infecting the model MRC strain Ruegeria pomeroyi DSS-3. Here, we show that not only do these phages have unusual substitution of deoxythymidine with deoxyuridine (dU) in their DNA, but they are also phylogenetically distinct from any currently known double-stranded DNA bacteriophages, supporting the establishment of a novel family (“Naomiviridae”). These dU-containing phages possess DNA that is resistant to the commonly used library preparation method for metagenome sequencing, which may have caused significant underestimation of their presence in the environment. Nevertheless, our analysis of Tara Ocean metagenome datasets suggests that these unusual bacteriophages are of global importance and more diverse than other well-known bacteriophages, e.g., the Podoviridae in the oceans, pointing to an overlooked role for these novel phages in the environment.
Jonathan Cook, Tyler C. Baverstock, Martin B.L. McAndrew, Phillip J. Stansfeld, David I. Roper, Allister Crow. (2020) Insights into bacterial cell division from a structure of EnvC bound to the FtsX periplasmic domain. PNAS.
The peptidoglycan layer is a core component of the bacterial cell envelope that provides a barrier to the environment and protection from osmotic shock. During division, bacteria must break and rebuild the peptidoglycan layer to enable separation of daughter cells. In E. coli, two of the three amidases responsible (AmiA and AmiB) are regulated by a single periplasmic activator (EnvC) that is, itself, controlled by an atypical ABC transporter (FtsEX) tethered to the cytoplasmic septal Z-ring. Here we define the structural basis for the interaction of FtsEX with EnvC and suggest a molecular mechanism for amidase activation where EnvC autoinhibition is relieved by ATP-driven conformational changes transmitted through the FtsEX-EnvC complex.
Smith O, Nicholson WV, Kistler L, Mace E, Clapham A, Rose P, Stevens C, Ware R, Samavedam S, Barker G, Jordan D, Fuller DQ, Allaby RG. (2019) A domestication history of dynamic adaptation and genomic deterioration in Sorghum. Nature Plants.
The evolution of domesticated cereals was a complex interaction of shifting selection pressures and repeated episodes of introgression. Genomes of archaeological crops have the potential to reveal these dynamics without being obscured by recent breeding or introgression. We report a temporal series of archaeogenomes of the crop sorghum (Sorghum bicolor) from a single locality in Egyptian Nubia. These data indicate no evidence for the effects of a domestication bottleneck, but instead reveal a steady decline in genetic diversity over time coupled with an accumulating mutation load. Dynamic selection pressures acted sequentially to shape architectural and nutritional domestication traits and to facilitate adaptation to the local environment. Later introgression between sorghum races allowed the exchange of adaptive traits and achieved mutual genomic rescue through an ameliorated mutation load. These results reveal a model of domestication in which genomic adaptation and deterioration were not focused on the initial stages of domestication but occurred throughout the history of cultivation.
Tildesley, MJ, Brand, S, Brooks Pollock, E, Bradbury, MV, Werkman, M & Keeling, MJ. (2019) The role of movement restrictions in limiting the economic impact of livestock infections. Nature Sustainability.
Livestock movements are essential for the economic success of the industry. However, these movements come with the risk of long-range spread of infection, potentially bringing infection to previously disease-free areas where subsequent localized transmission can be devastating. Mechanistic predictive models usually consider controls that minimize the number of livestock affected without considering other costs of an ongoing epidemic. However, it is more appropriate to consider the economic burden, as movement restrictions have major consequences for the economic revenue of farms. Here, using mechanistic models of foot-and-mouth disease, bluetongue virus and bovine tuberculosis in the UK, we compare the economically optimal control strategies for these diseases. We show that for foot-and-mouth disease, the optimal strategy is to ban movements in a small radius around infected farms; the balance between disease control and maintaining ‘business as usual’ varies between regions. For bluetongue virus and bovine tuberculosis, we find that the cost of any movement ban is greater than the epidemiological benefits due to the low within-farm prevalence and slow rate of disease spread. This work suggests that movement controls need to be carefully matched to the epidemiological and economic consequences of the disease, and that optimal movement bans are often of far shorter duration than allowed under existing policy.
|Compounds made from ‘digested’ molecules feeds appetite for greener pharmaceuticals and agrochemicals
A method of producing vital chemical building blocks for use in the pharmaceutical and agrochemical industries that mimics how plants manufacture them has been developed by a team at the Warwick Integrative Synthetic Biology Centre (WISB). The new method uses enzymes to produce indolic amides, carboxylic acids and auxins – vital for use in pharmaceutical and agrochemical industries.
Press Release (1 February 2022)
|Poolbeg Pharma licences RNA-based immunotherapy for respiratory virus infections
Poolbeg Pharma has in-licenced a novel, first-in-class RNA-based immunotherapy for respiratory virus infections. This dual action immunotherapy was developed at Warwick and derived from twenty years of research with Professor Andrew Easton and Professor Nigel Dimmock.
Press Release (17 January 2022)
|New framework to help assess what might be required to eliminate African sleeping sickness by 2030
An international group of researchers have created a new health economic framework that supports decision makers and funders in understanding the resources required to achieve the World Health Organization’s (WHO) goal of eliminating sleeping sickness by 2030.
Press release (13 December 2021)
|Starving Tuberculosis (TB) of sugars may be a new way to fight it
Tuberculosis is a devastating disease that claims over 1.5 million lives each year. The increase in TB cases that are resistant to the current antibiotics means that novel drugs to kill Mycobacterium tuberculosis (Mtb) are urgently needed. Dr Elizabeth Fullam and colleagues have successfully discovered how Mycobacterium tuberculosis uses an essential sugar called trehalose, which provides a platform to design new and improved TB drugs and diagnostic agents.
Press Release (15 April 2021)
|How bacterial traffic jams lead to antibiotic-resistant, multilayer biofilms
New insight on the physical interactions that take place between swarming bacteria when exposed to antibiotics could lead to novel approaches for treating infections in patients, shows a study by Dr Munehiro Asally and colleagues.
Press Release (16 March 2021)
|Identified: A mechanism that protects plant fertility from stress
As temperatures rise due to global warming the need to protect plants from stressful conditions has increased, as stress can cause a loss in yield and cause further impact economically. A consortium led by Professor Jose Gutierrez-Marcos have successfully identified two proteins that protect crops from stress, which is key in safeguarding food production.
Press Release (1 March 2021)
|Soil bacteria hormone discovery provides fertile ground for new antibiotics
Research by Dr Chris Corre and colleagues could lead to improved manufacturing of existing antibiotics, and open up opportunities to discover new ones.
Press Release (3 Feb 2021)