Latest Publications
Inflammation modifies breathing phenotype in mice with epilepsy
Amol Mohan Bhandare, Adwoa Boaten, Dylan Dunkwu, Jade Hill, Biborka Balazs, Nicholas Dale
Impaired CO₂ responsiveness in epilepsy can result in hypoventilation and hypercapnia and these respiratory disturbances are key contributors to Sudden Unexpected Death in Epilepsy (SUDEP). While mild to moderate inflammation is known to modulate respiratory function, its specific role in regulating respiratory responses in the context of epilepsy remains unclear. We studied the effects of lipopolysaccharide (LPS)-induced inflammation and microglial inhibition via minocycline during the acute and chronic phases of epilepsy on hypercapnic ventilatory responses (HCVR) in the intrahippocampal kainic acid model of temporal lobe epilepsy in male C57BL/6 mice. LPS treatment during acute seizures and minocycline during spontaneous seizures in the chronic phase of epilepsy restored the impaired HCVR in mice. Notably, LPS treatment during acute seizures also reduced the frequency of spontaneous seizures. In contrast, minocycline given during acute seizures and LPS administered during chronic epilepsy further exacerbated HCVR impairment. Immunohistochemical analysis of chemosensitive retrotrapezoid nucleus (RTN) revealed varied effects of different treatments in epileptic mice on microglia density, morphology and their expression of triggering receptor expressed on myeloid cells 2 (TREM2), P2Y12 receptor, and astrocytic adenosine 2A receptor (A2AR). Overall, the inflammation during epileptogenic or acute phase preserves HCVR and reduces spontaneous seizure frequency in chronic epilepsy, whereas in chronic phase it worsens HCVR. Although not yet fully validated, changes in microglial and astrocytic receptor expression could contribute to this HCVR impairment and may represent a mechanistic target for preserving HCVR in epilepsy; a dysfunction that could potentially lead to SUDEP.
Rapid local and systemic jasmonate signalling drives the initiation and establishment of plant systemic immunity
Trupti Gaikwad, Susan Breen, Emily Breeze, Erin Stroud, Rana Hussain, Satish Kulasekaran, Nestoras Kargios, Fay Bennett, Marta de Torres-Zabala, David Horsell, Lorenzo Frigerio, Pradeep Kachroo, Murray Grant
Successful recognition of pathogen effectors by plant disease resistance proteins, or effector-triggered immunity (ETI), contains the invading pathogen through localized hypersensitive cell death. ETI also activates long-range signalling to establish broad-spectrum systemic acquired resistance (SAR). Here we describe a sensitive luciferase (LUC) reporter that captures the spatial–temporal dynamics of SAR signal generation, propagation and establishment in systemic responding leaves following ETI. JASMONATE-INDUCED SYSTEMIC SIGNAL 1 (JISS1) encodes an endoplasmic-reticulum-localized protein of unknown function. JISS1::LUC captured very early ETI-elicited SAR signalling, which surprisingly was not affected by classical SAR mutants but was dependent on calcium and was also wound responsive. Both jasmonate biosynthesis and perception mutants abolished JISS1::LUC signalling and SAR to Pseudomonas syringae. Furthermore, we discovered that ETI initiated jasmonate-dependent systemic surface electrical potentials. These surface potentials were dependent on both glutamate receptors and JISS1, despite neither JISS1 loss-of-function nor glutamate receptor mutants altering SAR to Pseudomonas syringae. We thus demonstrate that jasmonate signalling, usually associated with antagonism of defence against biotrophs, is crucial to the rapid initiation and establishment of SAR systemic defence responses (including the activation of systemic surface potentials) and that JISS1::LUC serves as a reporter to further dissect these pathways.
A modelling assessment of the impact of control measures on highly pathogenic avian influenza transmission in poultry in Great Britain
Christopher N. Davis, Edward M. Hill, Chris P. Jewell, Kristyna Rysava, Robin N. Thompson, Michael J. Tildesley
Since 2020, large-scale outbreaks of highly pathogenic avian influenza (HPAI) H5N1 in Great Britain have resulted in substantial poultry mortality and economic losses. Alongside the costs, the risk of circulation leading to a viral reassortment that causes zoonotic spillover raises additional concerns. However, the precise mechanisms driving transmission between poultry premises and the impact of potential control measures in Great Britain, such as vaccination, are not fully understood. We have developed a spatial transmission model for the spread of HPAI in poultry premises calibrated to infected premises data for the 2022–23 season using Markov chain Monte Carlo. Our results indicate that reducing the susceptibility of the premises surrounding an identified infected premises (for example, through enhanced biosecurity measures and/or vaccination) can substantially reduce the overall number of infected premises. Our findings highlight that enhanced control measures could limit the future impact of HPAI on the poultry industry and reduce the risk of broader health threats.
From the lens of early-career researchers: bridging science, technology, arts, and humanities to tackle antimicrobial resistance
Nikhil Bhalla, Mojgan Rabiey, Prachi Bendale, Katie Lawther, Janice Spencer, Alberto Longo, Lucky Lucky, Vishal Chaudhary, Paul McCormack, Saikat Jana, Patrick S. M. Dunlop, Linda Oyama
Antimicrobial resistance (AMR) is a silent pandemic that presents a global challenge, urging researchers to develop innovative and transdisciplinary solutions. Our initiative aims to promote collaboration across science, engineering, economics, social sciences, and the arts to address the complex dimensions of AMR. We highlight the unique role of early-career researchers (ECRs) in advancing such cross-cutting approaches and conclude that empowering ECRs through equitable support and recognition is essential to sustaining innovation and mobilising communities against AMR.
Identification of evidence gaps and future research needs in food safety
Neuroimmune Regulation by TRPM2 Channels
Xuming Zhang, Mitali Malhotra
Mutual interaction between the nervous and immune systems underpins many pathophysiological processes. Transient Receptor Potential Melastatin 2 (TRPM2) channels are abundantly expressed in both systems, acting as a critical interface of neuroimmune interaction. TRPM2 channels in immune cells participate in innate immunity and immune inflammation by acting as an oxidative stress and metabolic sensor. TRPM2 in neurons functions not only as an oxidative sensor but also a temperature sensor and a pain transducer critical to neuronal death, temperature sensing, thermoregulation, and chronic pain. Cooperation between immune and neuronal TRPM2 influences the outcome of neuroimmune interaction and many diseases such as infection, inflammation, ischemic stroke, pain, and neurodegenerative diseases. Improved understanding of neuronal and immune TRPM2 interaction is essential for therapeutic interventions for the treatment of diseases mediated by TRPM2 channels.