MRC Centre for Inflammation Research Newsletter
November 2016
Welcome to the Centre of Inflammation Research Newsletter to keep you up-to-date with what is happening in the Centre.
In this Newsletter:
- Staff/Students
- News
- Equipment
- Press Releases
- Publications
- Grants
Staff/Students
Welcome
David Dockrell - Professor of Infection Medicine. David's research focuses on macrophage responses to infectious diseases with particular focus on respiratory infection. We are particularly interested in macrophage microbicidal responses and cell death paradigms in clearing pathogens. Clinical interests include opportunistic infections in immunocompromised hosts.
Debby Bogaert - Scottish Senior Clinical Fellow and Honorary Consultant in Paediatric Infectious Diseases. Debby's current research centres around understanding pathogenesis of respiratory infectious and inflammatory diseases from an ecological perspective. With this knowledge the ultimate aim to improve diagnostic, treatment and preventive strategies.
Jenna Cash – Chancellor's Fellow and Sir Henry Dale Fellow. Jenna's research focusses on understanding the events that determine whether a skin wound will heal acutely or develop into a chronic non-healing wound.
Jordan Portman – PhD student with Professor Neil Henderson's group. Jordan's project is entitled 'A single-cell sequencing approach to identify new therapeutic targets to drive liver regeneration'.
Sam Benson – PhD student with Marc Vendrell's group. Sam's project is entitled 'Novel theranostic agents for enhanced diagnosis and minimally invasive therapy of cervical cancer'.
Joanna Long – PhD student with Kev Dhaliwal's group. Joanna is working on the Optima project.
Jessie May Morgan –PhD student with Sarah Walmsley's group. Her project title is 'Super resolution imaging of the neutrophil cytoskeleton'.
Dominic Norberg – PhD student with Kev Dhaliwhal's group. His project title is 'Fetal monitoring during childbirth'.
Valentina Rausch – PhD student with Carsten Hansen's group. Valentina's project title is 'Cellular regulation of and by the Hippo pathway: Cancer and Regeneration'.
Siobhan Rice – PhD student with Professor Elaine Dzierzak's group. Her project title is 'Understanding the role of macrophages in HSC development in the mouse embryo'.
Roger Ronn – Postdoc with Professor Elaine Dzierzak's group. Roger's research title is 'Enhancing hematopoietic stem cell growth: manipulation of hypoxia and oxidative stress conditions'.
Barry McCormick – Postdoc with Sonja Vermeren's group working on'Integrin activation in neutrophils in autoimmune disease'.
Jody Van Engelsdorp–Research Assistant with Professor Debby Bogaert's group.
Maria Panagopoulou–Optima PhD student with Professor Chris Gregory's group working on Extracellular Vesicles (Exosomes).
RaizaHasrat – PhD student with Professor Debby Bogaert's group. Raiza is studying the interaction between pathogens, commensal and human epithelial cells.
Nikolay Ogryzko– Postdoc Fellow with Dr Feng's group. Nikolay is working on the role of NF-kB signalling in tumour promoting inflammation.
Mari Pattison–Mari has joined the flow cytometry laboratory.
David Taggart – PhD student with Professor Anderton/Dr Serrels' laboratory and his project title is 'Inflammatory mechanisms to suppress T-Reg cell function in cancer'.
PhD Vivas
Congratulations to Lauren Patience in Professor Chris Gregory's group for passing her viva on 7 September. Her project title was 'Apoptosis-driven microenvironmental conditioning by microvesicles in non-Hodgkin lymphoma'.
Congratulations to CharaCharsou in Professor Sarah Howie's group for passing her viva on 8 September. Her project title was 'Autophagy regulation in human papillomavirus infection'.
Congratulations to Alex Thompson in Professor Neil Henderson'sgroup for passing her viva on 10 October. Her project title was ‘Investigation of the role of hepatic stellate cells in acute liver failure and hepatocarcinogenesis'.
News
Congratulations to Dr Emily Gwyer Findlay (September 2016)
Emily Gwyer Findlay has been successful in obtaining a highly prestigious Dorothy Hodgkin fellowship from the Royal Society. Her project is entitled "Cathelicidin is critical for pathogenic T cell development in multiple sclerosis"' and she is going to work in association with Donald Davidson and Steve Anderton.
NRS/Universities Scottish Senior Clinical Fellowships (October 2016)
The CIR is delighted to announce that two of its members, Debby Bogaert and Robert Gray, have been appointed to highly competitive five year Scottish Senior Clinical Fellowships. Many congratulations are given to them on their success.
University deal gives boost to disease research (October 2016)
The licence agreement between life sciences giant Merck and the University of Edinburgh’s commercialisation arm, Edinburgh Research & Innovation involving technology will help research around the world to understand how diseases progress in their early stages.
The technology is based on using natural peptide mimics as “disease reporters” by applying a fluorescent compound or re-agent that makes them easier to identify. Academics at Edinburgh’s School of Clinical Sciences, led by Dr Marc Vendrell (CIR), carried out the research alongside partners at The University of Barcelona and The University of Manchester. Dr Vendrell said the fluorescent reagent is so powerful it can allow scientists to see very small differences between healthy and diseased cells, which in turn can have a big impact on diagnosis and treating diseases.
The Herald Scotland article
Equipment
We recently purchased an Ecomax x-ray film developer which has replaced our old film developer (W2.31). This is in addition to the Licor c-digit chemiluminescence western blot scanner already present in E2.25. Please contact Steven McLean or Pat Swan to arrange training before first use.
Further details on the Ecomax and C-Digit can be found on the following links:
Ecomax -
Licor C-Digit -
Press Releases
Skin’s own defences point towards new eczema therapies (October 2016)
The body’s own natural defences could be harnessed in a potential therapy for a common skin condition, research suggests. The discovery may help create new treatments for atopic eczema, which affects around one in five children and one in 20 adults in the UK.
Researchers at the MRC Centre for Inflammation Research have discovered that skin cells can be instructed to produce a naturally occurring protective compound. This substance – called human beta-defensin 2 (hBD2) – is known to kill bacteria, but the study found it is also vital in preventing damage to the skin barrier caused by Staphylococcus aureus. Individuals with eczema typically do not turn on production of hBD2 in their damaged skin lesions.
The researchers found that when hBD2 was applied to skin cells grown in the lab, it helped the skin to remain intact, with the cells strengthening protection against the bacterial damage like reinforcing mortar between the bricks in a wall. Their findings could lead to new therapies to prevent or treat eczema. Conventional treatment with steroid creams can have side-effects, and become less effective over time.
The study is published in the Journal of Investigative Dermatology. The work was funded by the Medical Research Council and China Scholarship Council.
For more information:
Published paper
University Press Release
BBC
Scotsman
Immune cell insight offers hope for tackling deadly lung condition (November 2016)
Fresh insights into a life-threatening lung condition triggered by blood poisoning could signal a new approach to treating the disease, researchers found. Scientists have found that a drug, which targets key immune cells, could help to curb excessive inflammation in the lungs that is linked to the condition. The researchers say more studies are needed, but their findings from tests on patients’ cells are promising. Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition caused by an overwhelming influx of a type of immune cell into the lungs during an infection. These cells – called neutrophils – are initially brought in to fight the infection but they can also inflict significant damage on the lung. At the end of an infection, neutrophils usually self-destruct in a controlled manner to prevent bystander damage to healthy tissues. In ARDS, the cells survive for longer and this is thought to contribute to a worsening of the condition.
Researchers at the MRC Centre for Inflammation Research sought to investigate whether targeting neutrophils could offer a useful approach to treating the condition.They found that treating neutrophils taken from patient blood samples with a drug called AT7519 helped to restore the cells’ normal self-destruct process. After 20 hours of treatment in the laboratory, the cells behaved like those of healthy people. The findings suggest that AT7519 could offer a useful therapy to resolve inflammation in the lung in patients with ARDS. ARDS results in severe breathing difficulties that requires treatment in intensive care. Up to half of people who develop the condition do not survive as there are currently no effective treatments. Patients are usually placed on a ventilator to help them breathe until the inflammation resolves. AT7519 belongs to a family of drugs called cyclin-dependent kinase inhibitors and is currently being trialled as a cancer therapy. More studies are needed but researchers are optimistic that AT7519 could eventually be tested as a treatment for ARDS in patients.
The study, by the Medical Research Council Centre for Inflammation Research, is published in the journal Thorax.
Published paper (Thorax Journal website -
Publications
Docherty A, Anderson N, Walsh T, Lone N. 'The authors reply: Patient-centred outcomes for the critically ill elderly patient'. Critical Care Medicine 2016, vol 44, no 8, 10.1097/CCM.0000000000001903, 01/08/16
Seth S, Akram AR, McCool P, Westerfeld J, Wilson D, McLaughlin S, Dhaliwal K, Williams CKI. 'Assessing the utility of autofluorescence-based pulmonary optical endomicroscopy to predict the malignant potential of solitary pulmonary nodules in humans'. Scientific Reports 2016, vol 6, 31372, 10.1038/srep31372, 23/08/16
Murray IR, Baily J, Chen WCW, Dar A, Gonzalez ZN, Jensen AR, Petrigliano FA, Deb A, Henderson NC. 'Skeletal and Cardiac Muscle Pericytes: Functions and Therapeutic Potential'. Pulmonary pharmacology & therapeutics 2016, 10.1016/j.pharmthera.2016.09.005, 02/09/16
Prost S, Kishen REB, Kluth D, Bellamy C. 'Choice of Illumination system & fluorophore for multiplex immunofluorescence on FFPE tissue sections'.PLoS One 2016, vol 11, no. 9, pp. e0162419, 10.1371/journal.pone.0162419, 15/09/16
Prost S, Kishen REB, Kluth , Bellamy C. 'Working with Commercially Available Quantum Dots for Immunofluorescence on Tissue Sections'.PLoS One 2016, vol 11, no. 9, pp. e0163856, 10.1371/journal.pone.0163856, 30/09/16
Chu JY, Dransfield I, Rossi A,Vermeren S. 'Non-canonical PI3K – Cdc42 – Pak – ErkSignaling Promotes Immune Complex Induced Apoptosis in Human Neutrophils'. Cell Reports 2016, 10.1016/j.celrep.2016.09.006, 04/10/16
Schwarze J, Fitch P, Heimweg J, Errington C, Matsuda R, de Bruin HG, van der Berge M, van Oosterhout AJM, Heijink IH. 'Viral mimic poly-(I:C) attenuates airway epithelial T cell suppressive capacity; implications for asthma'. European Respiratory Journal 2016, 10.1183/13993003.00841-2016, 06/10/16
Martin K, Pritchett J, Llewellyn J, Mullan AF, Athwal VS, Dobie R, Harvey E, Zeef L, Farrow S, Streuli C, Henderson NC, Friedman SL, Hanley NA, Hanley KP. 'PAK proteins and YAP-1 signalling downstream of integrin beta-1 in myofibroblasts promote liver fibrosis'. Nature Communications 2016, vol 7, 12502, 10.1038/ncomms12502, 18/08/16
Kauts M-L, Vink CS, Dzierzak E. 'Hematopoietic (stem) cell development-how divergent are the roads taken?'.FEBS Letters 2016, 10.1002/1873-3468.12372, 20/08/16
Nasrallah R, Fast EM, Solaimani P, Knezevic K, Eliades A, Patel R, Thambyrajah R, Unnikrishnan A, Thoms J, Beck D, Vink CS, Smith A, Wong J, Shepherd M, Kent D, Roychoudhuri R, Paul F, Klippert J, Hammes A, Willnow T, Göttgens B, Dzierzak E, Zon LI, Lacaud G, Kouskoff V, Pimanda JE. 'Identification of novel regulators of developmental hematopoiesis using endoglin regulatory elements as molecular probes'. Blood 2016, 10.1182/blood-2016-02-697870, 23/08/16
Jackson-Jones L, Duncan S, Magalhaes M, CampbellS, Maizels R, McSorley H, Allen J, Benezech C.'Fat associated lymphoid clusters control local IgM secretion during pleural infection and lung inflammation'. Nature Communications 2016, 10.1038/ncomms12651, 01/09/16
Haldar D, Henderson NC, Hirschfield G, Newsome PN. 'Mesenchymal stromal cells and liver fibrosis: a complicated relationship'. The FASEB Journal 2016, 10.1096/fj.201600433R, 06/09/16
Wang B, McHugh B, Qureshi A, Campopiano D, Clarke D, Fitzgerald J, Dorin J, Weller R, Davidson D. 'IL-1beta-induced protection of keratinocytes against Staphylococcus aureus-secreted proteases is mediated by human beta defensin 2'. Journal of Investigative Dermatology 2016, 10.1016/j.jid.2016.08.025, 01/10/16
Boyapati RK, Ho GT, Satsangi, J. 'Can Thiopurines prevent formation of antibodies against tumornecrosis factor antagonists after failure of these therapies' Clinical Gastroenterology and Hepatology 2016, 10.1016/j.cgh.2016.09.152, 05/10/16
Zhao C, Fernandez A, Avlonitis N, VandeVelde G, Bradley M, Read ND, Vendrell M. 'Searching for the Optimal Fluorophore to Label Antimicrobial Peptides' ACS Combinatorial Science 2016, 10.1021/acscombsci.6b00081, 10/10/16
Dorward D, Felton JM, Robb C, Craven T, Kipari T, Walsh T, Haslett C, Kefala K, Rossi A, Lucas C. 'The cyclin-dependent kinase inhibitor AT7519 accelerates neutrophil apoptosis in sepsis-related acute respiratory distress syndrome' Thorax 2016, 10.1136/thoraxjnl-2016-209229, 24/10/16
Grants
Pulmonary epithelial barrier and immunological functions at birth and in early life – key determinants of the development of asthma
Wellcome Trust
Prof Jurgen Schwarze
3 yrs – Strategic award
£296,905
Ultraviolet A as a treatment for mild hypertension
British Heart Foundation
DrRichard Weller
3yrs – Research grant
£252,384
Characterization of the immune population after phototherapy in AD patients
British Skin Foundation
Dr Anne Astier
3yrs – Research general scheme
£9,600
New chemical imaging probes for real-time detection of apoptosis and enhanced monitoring of inflammatory diseases
Royal Society
Dr Marc Vendrell
1 yr – Research grant
£15,000
Investigating impaired alveolar macrophage function in COPD: is the phenotype a consequence of defective cellular metabolism?
Wellcome Trust
Dr Eilise Ryan
2yrs – Research Training Fellowship
£176,791
Quantitative and anatomical definition of kynurenine metabolism in rodents during systemic inflammation
RCS England
Dr Damian Mole
1yr – Studentship
£5,000
Androgens and women's health: developing new therapies to treat endometrial disorders
Medical Research Council
Prof Philippa Saunders
5yrs – Population and Systems Medicine Board
£1,423,505
Novel theranostic agents for enhance diagnosis and minimally invasive therapy of cervical cancer
SHERT Medical Research Scotland
Dr Marc Vendrell
4 yrs – Studentship
£107,677
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