In an exciting new paper led by STRAND Researchers Dr Bhavik Patel, Dr Mel Flint and Dr Mark Yeoman, alongside colleagues from The Open University examining a potential novel treatment class for chronic constipation has been published in the prestigious Nature Scientific Reports. The paper examines the use of 5-HT, an important pro-kinetic agent in the colon, to see if alterations in colonic 5-HT signalling underlie age–related changes in faecal output in mice and whether these changes were due to an increase in TNF-α. The researchers observed reduced faecal output and water content in aged animals, as well as increased mucosal 5-HT availability and TNF-α expression and decreased mucosal SERT expression and 5-HIAA. The treatment of old mice with Etanercept reversed these changes, suggesting that age-related changes in TNFα expression are an important regulator of mucosal 5-HT signalling and pellet output and water content in old mice. This study points to “anti-TNFα” drugs as potential treatments for age-related chronic constipation.
Patel, BA, Fidalgo, S, Wang, C, Parmar, L, Mandona, K, Panossian, A, Flint, MS, Ranson, RN, Saffrey, MJ & Yeoman, MS (2017) The TNF-α antagonist etanercept reverses age-related decreases in colonic SERT expression and faecal output in mice. Sci. Rep. 7, 42754; doi: 10.1038/srep42754
Recent work by STRAND Member Kok Choi Kong has been published in the prestigious Proceedings of the National Academy of Sciences of the United States of America. The paper is important as studies in transfected cells have established that G protein-coupled receptors (GPCRs) activate a number of intracellular signaling pathways; however, which of these pathways are physiologically important is unclear. The authors use a genetically engineered mouse to demonstrate a novel role for M3-muscarinic acetylcholine receptor (M3-mAChR) phosphorylation in airway constriction, with implications for human respiratory disease, including asthma and chronic obstructive pulmonary disease. Combining this finding with other M3-mAChR physiological responses, the authors also generate a map of responses that are downstream of G protein-dependent signaling or receptor phosphorylation-dependent signaling. This map predicts the outcome of biased GPCR drugs designed to drive receptor signaling preferentially toward pathways that improve therapeutic efficacy while minimizing toxic/adverse outcomes and providing a fundamental approach to the rational design of next-generation GPCR-based therapies.
If you are interested in the paper, the reference can be found below:
Bradley, SJ, Wiegman CHC, Iglesias, MM, Kong KC, Butcher AJ, Goupil E, Bourgognon JM, Macedo-Hatch T, Russell K, Laporte SA, Kostenis E, Bouvier M, Chung KF, Amrani Y, Tobin AB (2016): Mapping physiological G protein-coupled receptor signalling pathways reveals role for receptor phosphorylation in airway contraction. Proc Natl Acad Sci U S A 113 (16), 4524-4529
Congratulations to MPharm Year 3 student, Prijay Bakrania, who has been awarded a Vacation Scholarship entitled ‘Does the expression of Nrf2 change with age in humans?’
The project, under the supervision of STRAND member Dr Greg Scutt, examines Nrf2 an important protein which controls a cells ability to breakdown toxins, poisons and some drugs. Research conducted over the past 10 years has found that the levels of this protein in animals declines with age. This may make older animals more susceptible to harm from these substances.
Dr Scutt said “We are not sure what happens to the levels of Nrf2 in humans, but if it also declines with age, then it could make older individuals more susceptible to the harmful effects of prescribed medications. The aim of this research is to establish whether the age effects the levels of Nrf2 in human white blood cells. We plan do this by taking a small sample of blood from volunteers of different ages and then measuring in white blood cells 1) the level of Nrf2 protein and 2) the level of messenger RNA which contains the code for the Nrf2 protein. There are several known factors which can affect Nrf2 levels, and we want to take these into account when analyzing the data. These include medical history and medication. Some individuals also have a slightly different genetic form Nrf2, or an associated protein called Keap-1 which can affect the activity of Nrf2 found in cells. We also plan to check which genetic form of these proteins volunteers possess so that they can be taken into consideration during the analysis. We also plan to measure the levels of Keap-1 messenger RNA and protein in white blood cells to determine if they change with age.”
STRAND Researchers have published a recent paper in Autonomic Neuroscience, with some of the work being done by BSc Pharamceutical Science students. The paper entitled “Acute paraquat exposure impairs colonic motility by selectively attenuating nitrergic signalling in the mouse” examined the effects of acute paraquat administration on colonic motility in the C57BL/6 mouse.
The study summarised that acute paraquat exposure attenuates colonic transit. These changes may facilitate the absorption of paraquat into the circulation and so facilitate its toxicity.
STRAND Members Dr Angela Sheerin & Dr Claire Marriott, along with PABS colleagues Dr Anna Guildford & Ms Bertie Berterelli, have been doing some outstanding outreach work. The full story can be seen below:
A* Scientist outreach work
STRAND is delighted to be hosting a series of talks, at 3pm on Wednesday 25th November in Watts House, by researchers from the Institute of Neuroscience a Physiology, at The Sahlgrenska Academy, University of Gothenburg. The talks will be given by Prof. Gunnar Tobin, and his research team from the Department of Pharmacology:
Prof. Gunnar Tobin: “Research at the Dept of Pharmacology – an overview”
Dr Michael Winder: “Regulation of nitric oxide in bladder epithelial cells”
Dr Thomas Carlsson: “Bladder dysfunction in animal models of Parkinson´s disease”
Dr Marie Kalm: “How can we prevent cognitive decline after brain tumour treatment?”
The Sahlgrenska Academy consists of 6 institutes, 2 units and 1 national centre that have attracted more than €90 million in external research funds. The 22 research centres that form the Academy are inter-disciplinary venues for Research, Training, the Private Sector and the General Community.
For more information please contact us here
STRAND researcher Dr Annamaria Gal is giving a talk to the Brighton and Sussex Cancer Network on Thursday 26th November. The seminar, entitled “Plasticity and recruitent of tumour associated macrophages in murine metastatic melanoma” will run from 4-6pm in the Medical Research Building, University of Sussex and involve a 50-minute talk followed by discussion and networking.
If you are interested in this seminar please contact Dr Gal, Sarah Newbury (S.Newbury@bsms.ac.uk) or Dr Melanie Flint.
The STRAND microbiology research team, led by Dr Brian Jones, have played a key role in developing a new “intelligent” wound dressing that responds to infection. Dr Jones and his team (from Univeristy of Brighton, Queen Victoria Hospital, and the Blond McIndoe Research Foundation) have been working as part of a group Universities and NHS Trusts across the South of England, led by Prof Toby Jenkins at the University of Bath, to develop this dressing technology. This will tell clinicians when a wound is infected through a simple colour change, and this initial study provides proof-of-concept for an advanced infection detecting dressing for wound care, which could allow the targeted treatment of infections at the bedside and reduce the unnecessary use of antibiotics. Dr Jones said: “This new dressing technology will not only help clinicians provide the best possible treatment for patients with burns, but could also tell us a lot about how wound infections begin and how they affect the normal healing process. This could in turn lead to even further advances in treating these infections”
For more information about this project please contact Dr Brian Jones or click here
The newly developed dressing
The dressing when a simulated infection is present