MRC Centre for Inflammation Research Newsletter

July 2016Welcome 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 Travel Public Engagement Press Releases Available Funding Publications Grants

Staff/Students

Welcome

Emma Bashford – PhD student has started with Prof Roberts and is studying ‘Microwave Radiometry’.

Dr Justin Killick – Postdoc has joined Dr Astier’s Group and will be working on ‘Molecular mechanisms controlling T cell migration in Multiple Sclerosis’.

Dr Pranvera Sadiku – Research fellow has joined Dr Walmsley’s Group and will be working on ‘The regulation of neutrophilic inflammation by the HIF/PHD2 oxygen sensing pathway’.

Wouter de Steenhuijsen Piters – visiting PhD student

PhD Vivas

Congratulations to Joanne Simpson in Dr Gray’s Group for passing her recent viva. Her project title was ‘Immune regulation induced by apoptotic cells in health and in systemic lupus erythematosus’.

Farewell

The CIR had a farewell drinks party and presentation for Dr Sharon Hannah on 20th May. All of the CIR would like to wish Sharon every success in her new role as BioQuarter Campus Operations Manager for the University of Edinburgh.

Travel

Train Travel Discount

Staff can save 20% on train journeys to London when travelling for work. The University, in partnership with Key Travel, has agreed a 20% discount on Virgin East Coast trains between Edinburgh and London.

FREE Travel Insurance

New online form for organising work related travel insurance for free. It is recommended that anyone travelling on behalf of the University (to conferences, meetings etc.) arranges travel insurance. Be aware your personal travel insurance may not cover work travel.

Cycles for Hire

UniCycles bike hire is for staff and students at the University of Edinburgh. UniCycles is being delivered in partnership with EUSA and with grant funding from Cycling Scotland.

Public Engagement@EdinUni_MeetCIR

MRC Festival of Medical Research

Researchers from the CIR have been involved in the inaugural MRC Festival of Medical Research (18th - 26th June 2016), visiting four local schools to trial "Supercytes" a new inflammation / immunology schools resource, in advance of the future launch. This incorporates a presentation, short video about the CIR, a series of short, fun immune cell animations, a card game, a quiz and a competition, complete with teacher's lesson plan integrated into the Curriculum for Excellence. Thanks to Cathy Hawley, Lisa Kelly, Phoebe Kirkwood, Donald Davidson and everybody else who has helped.

Boroughmuir High School – Science Careers event

Siobhan Crittenden and Lara Campana represented the University of Edinburgh/ MRC Centre for Inflammation Research at Boroughmuir High School’s ‘Speed Date a Scientist’ science career’s event on the evening of 15th June 2016. This event gave students in their final year of school a chance to have short informal discussions with a range of visitors at different stages in STEM field careers. The pupils all seemed to enjoy the evening. They came to realise that not everyone has a direct career path and that there is great variety in science related careers.

Siobhan Crittenden (CIR PhD student) “The pupils were interested in my academic path, which had resulted in a PhD position, and how I had made the decisions at each stage to get here.”

Pupil comments:

“The event opened my eyes to the vast number of job opportunities there are from studying a science at university. Talking to them about how they go to where they are was really useful”

“I now have a better idea of jobs I would like to do”

“Puts a lot of what you are learning in to the context of the real world. And helps A LOT with future plans”

“Builds confidence in your ability to talk to others, that you have never met before”

Press ReleasesImmune study offers treatment hope for arthritis patients (April 2016)

Arthritis and other inflammatory conditions could be helped by new insights into how the immune response is switched off. Scientists lead by Dr Mohini Gray have discovered how compounds produced by the body’s immune system help to dampen inflammation and prevent damage to healthy tissues.

Their findings suggest that therapies based on these compounds could help to treat rheumatoid arthritis, which occurs when the immune system attacks the joints, causing pain and swelling. The research could also lead to new treatments for sepsis, where a body-wide immune response causes life-threatening tissue damage.

The compounds called alpha defensins are part of the body’s first line of defence against infection. They help to stop bacteria and other infectious agents from reproducing. Studies have suggested that the compounds may also act on cells of the immune system to prevent excessive inflammation but until now it was not clear how the process works.

In a study involving human cells, researchers at the University of Edinburgh have shown that alpha defensins are released by immune cells called neutrophils when they die. The alpha defensins are then taken up by other immune cells called macrophages. The team found that the compounds prevent macrophages from producing messenger molecules called cytokines, which drive inflammation.

The overall effect is to limit excessive inflammation, restricting damage to healthy tissues without compromising the body’s ability to clear the infection. These findings could lead to new treatments for chronic inflammatory disorders including rheumatoid arthritis. Such therapies could even prevent the condition from flaring-up in the first place, the team predicts.

The study, funded by the Medical Research Council and Arthritis UK, is published in the journal Proceedings of the National Academy of Sciences.

Study seeks to explore health benefits of vitamin D (May 2016)

Research lead by Dr Richard Mellanby is taking place to investigate the effects of vitamin D on the health of pet dogs. Studies have begun to better understand how dogs acquire vitamin D, which has been linked to animal health and wellbeing. Researchers also hope to learn more about whether it has any benefits for animals recovering from surgery.

In the first of the studies, vets are assessing pet dogs that have had surgery to repair damage to their knee ligaments. All of the animals involved in the research have been injured spontaneously, typically while on a walk with their owners.

Previous studies have shown that animals with lower levels of vitamin D in their blood often show signs of increased inflammation. Researchers will examine whether inflammation linked to reduced vitamin D can hamper dogs’ recovery from surgery. Blood samples will be taken before and after surgery to allow the team to measure vitamin D and any symptoms of inflammation.

The team will then monitors the dogs to see whether having higher levels of vitamin D before surgery has a positive effect on their recovery. If a link is found, researchers will test if vitamin D supplements can help to lower inflammation and improve chances of better recovery from surgery.

In a separate study, vets will investigate how dogs acquire vitamin D in the first place. It is widely thought that dogs get most of their vitamin D from their diet. The research will explore whether dogs can also produce vitamin D in their skin after exposure to the sun, in the same way that people do. The findings will help to determine whether dogs are getting enough vitamin D in their diet throughout the year.

All of the dogs taking part are owned by local people who have given permission for their pets to be studied and the research is tightly regulated.

Congratulations to Dr Sharon Hannah on her ‘BEM’ (June 2016)Dr Sharon Hannah was awarded a British Empire Medal "For services to medical research" in the 2016 Birthday Honours list. The British Empire Medal is a British medal awarded for meritorious civil or military service worthy of recognition by the Crown.Since being appointed manager of the Rayne Laboratory in 1994 Sharon has worked tirelessly and very effectively for the University; as MRC/UoE CIR manager, QMRI manager, and now as University BioQuarter Campus Operations Manager. Not long ago she was also awarded the "Hawksbee Medal" of the Royal Society (London) for services in support of science.

University of Edinburgh researchers win prestigious Royal Society of Chemistry Award (June 2016)The UoE/GSK KMO DPAc team (Chris Mowat - Chemistry, Scott Webster - CVS, and Damian Mole - CIR/Surgery) travelled to London to receive the ‘Teamwork in Innovation Award', at the Royal Society of Chemistry Industry and Technology Awards 2016. Congratulations to Dr Jenna Cash (June 2016)Dr Jenna Cash, recently appointed to a Chancellor's Fellowship based in the CIR and the new Centre for Tissue Regeneration and Repair, has been awarded a Sir Henry Dale Fellowship. In partnership between the Royal Society and the Wellcome Trust, the scheme provides support for postdoctoral researchers who aim to become independent scientists leading their own groups.

Congratulations to Honorary Professor Adam Hill (June 2016)Adam Hill, Consultant Respiratory Physician in NHS Lothian, has been awarded an Honorary Professorship in Respiratory Medicine at the University of Edinburgh. This is in recognition of his work in bronchiectasis, which incorporates work in the CIR undertaken in collaboration with Professor Adriano Rossi, Dr Donald Davidson and others.

Congratulations to Professor Philippa Saunders (June 2016)Professor Philippa Saunders has played an important role as a member of the Academy of Medical Sciences expert working group on ‘Team Science’ which reported in March of this year. The report called for more transparent reward systems in scientific research otherwise there was a risk that aspiring researchers might shun large collaborations.

Peritoneal macrophages progressively derive from BM monocytes as animals age but the process is gender-dependent (June 2016) Macrophages are immune cells that reside in all organs of the body where they play a key role in maintaining healthy tissues by responding to infection and injury and clearing away dying cells. Like most immune cells, tissue macrophages were thought to be continually replenished from bone marrow-derived cells that circulate in the blood. However, recently it has been proposed that while

some macrophages come from the blood during inflammation, those that reside in many tissues come from cells that entered the tissue during embryo development, and subsequently survive for years by local self-replication. This raises many questions about how mature macrophages could survive for such an extensive period, particularly without becoming harmful to the body through accumulation of damage to their DNA that can occur with self-replication. This study published in Nature Communications lead by Dr S. Jenkins, used multiple cell tracking techniques to determine exactly macrophages that are present in the body cavities are maintained. They found that although the peritoneal cavity was initially populated with embryo-derived macrophages during embryonic development, these were gradually replaced by cells (monocytes) from the bone marrow as animals aged. No evidence was found that this change in make-up of the population was due to a degeneration in the ability of embryo-derived cells to self-renew but did find that it inherently led to a subtle change in nature of the population as animals aged. Unique to the peritoneal cavity, they also found that the rate at which this switch in origin occurred was dramatically different between male and female mice, potentially explaining why inflammatory responses in this site are largely more effective in females than males.

Available Funding

Inviting projects for MSc students, £10,000 of consumables to the group hosting the research project. The projects are for ten months starting in November 2016 and should have two supervisors from separate disciplines related broadly to genomics, informatics, imaging and molecular pathology. It is expected that supervisors who wish to host a student should make their laboratory available to prospective students for a one week “taster” project during August or September, at the start of the course.

If interested send Tim Aitman (tim.aitman@ed.ac.uk) and Simon Herrington MSc course director (simon.herrington@ed.ac.uk) project descriptions (5-10 lines) of potential projects that you might wish to supervise students for in the coming year, with justification of the £10,000 consumables tag attached.

Publications

McBride O, Joshi N, Robson JM, MacGillivray T, Gray C, Fletcher AM, Dweck M, van Beek E, Rudd JH, Newby D, Semple S. 'Positron emission tomography and magnetic resonance imaging of cellular inflammation in patients with abdominal aortic aneurysms.' European Journal of Vascular and Endovascular Surgery 2016, vol 51, no. 4, 10.1016/j.ejvs.2015.12.018, 1/4/16

Jones HR, Robb CT, Perretti M, Rossi AG. 'The role of neutrophils in inflammation resolution' Seminars in immunology 2016, 10.1016/j.smim.2016.03.007, 1/4/16

Szkolnicka D, Lucendo Villarin B, Moore J, Simpson K, Forbes S, Hay D. 'Reducing hepatocyte injury and necrosis in response to paracetamol using non-coding RNAs' Stem cells translational medicine 2016, 10.5966/sctm.2015-0117, 7/4/16

Nolan TJ, Gadsby NJ, Hellyer TP, Templeton KE, McMullan R, McKenna JP, Rennie J, Robb CT, Walsh TS, Rossi AG, Conway Morris A, Simpson AJ. 'Low-pathogenicity mycoplasma spp. alter human

monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia' Thorax 2016, 10.1136/thoraxjnl-2015-208050, 12/4/16

Robertson AL, Ogryzko NV, Henry KM, Loynes CA, Foulkes MJ, Meloni MM, Wang X, Ford C, Jackson M, Ingham PW, Wilson HL, Farrow SN, Solari R, Flower RJ, Jones S, Whyte MK, Renshaw SA. 'Identification of benzopyrone as a common structural feature in compounds with anti-inflammatory activity in a zebrafish phenotypic screen' Disease Models & Mechanisms 2016, doi: 10.1242/dmm.024935, 14/4/16

Wilson K, Auer M, Binnie M, Zheng X, Pham N, Iredale J, Webster S, Mole D. 'Overexpression of human kynurenine-3-monooxygenase protects against 3-hydroxykynurenine-mediated apoptosis through bidirectional non-linear feedback' Cell Death and Disease 2016, vol 7, e2197., 10.1038/cddis.2016.87, 14/4/16

Griffith D, Lewis S, Rossi A, Rennie J, Salisbury L, Merriweather JL, Templeton K, Walsh T, RECOVER Investigators. 'Systemic inflammation after critical illness: relationship with physical recovery and exploration of potential mechanisms' Thorax 2016, 10.1136/thoraxjnl-2015-208114, 26/4/16

Krstajic N, Akram AR, Choudhary TR, McDonald N, Tanner MG, Pedretti E, Dalgarno PA, Scholefield E, Girkin JM, Moore A, Bradley M, Dhaliwal K. 'Two-color widefield fluorescence microendoscopy enables multiplexed molecular imaging in the alveolar space of human lung tissue' Journal of Biomedical Optics 2016, vol 21, no. 4, 046009., 10.1117/1.JBO.21.4.046009, 27/4/16

Robb C, Regan KH, Dorward D, Rossi A. 'Key mechanisms governing resolution of lung inflammation' Seminars in Immunopathology 2016, 10.1007/s00281-016-0560-6, 27/4/16

McAvoy N, Semple S, Richards JMJ, Robson AJ, Patel D, Jardine AGM, Leyland K, Cooper AS, Newby D, Hayes P. 'Differential visceral blood flow in the hyperdynamic circulation of patients with liver cirrhosis' Alimentary Pharmacology and Therapeutics 2016, 10.1111/apt.13571, 1/5/16

Betz B, Jenks SJ, Cronshaw A, Lamont DJ, Cairns C, Manning J, Goddard J, Webb D, Mullins J, Hughes J, McLachlan S, Strachan MWJ Price J, Conway B. 'Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes' Kidney International 2016, vol 89, no. 5, pp. 1125–1135., 10.1016/j.kint.2016.01.015, 1/5/16

Rabinovich R, Miller BE, Wrobel K, Ranjit K, Williams MC, Drost E, Edwards LD, Lomas DA, Rennard SI, Agusti A, Tal-Singer R, Vestbo J, Wouters EFM, John M, van Beek E, Murchison JT, Bolton CE, MacNee W, Huang JTJ. 'Circulating desmosine levels do not predict emphysema progression but are associated with cardiovascular risk and mortality in COPD' European Respiratory Journal 2016, 10.1183/13993003.01824-2015, 1/5/16

Cousins FL, Kirkwood PM, Murray AA, Collins F, Gibson DA, Saunders PTK. 'Androgens regulate scarless repair of the endometrial "wound" in a mouse model of menstruation' The FASEB Journal 2016, 10.1096/fj.201600078R, 2/5/16

Conroy K, Kitto L, Henderson N. 'αv integrins: key regulators of tissue fibrosis' Cell and tissue research 2016, 10.1007/s00441-016-2407-9, 2/5/16

Wagenfeld A, Saunders P, Whitaker L, Critchley H. 'Selective progesterone receptor modulators (SPRMs): Progesterone receptor action, mode of action on the endometrium and treatment options

in gynaecological therapies.' Expert Opinion on Therapeutic Targets 2016, 10.1080/14728222.2016.1180368, 3/5/16

Coutinho A, Kipari T, Zhang Z, Esteves C, Lucas CD, Gilmour JS, Webster S, Walker B, Hughes J, Savill J, Seckl J, Rossi A, Chapman K. '11β-Hydroxysteroid Dehydrogenase type 1 is expressed in neutrophils and restrains an inflammatory response in male mice' Endocrinology 2016, 10.1210/en.2016-1118, 4/5/16

Mills B, Bradley M, Dhaliwal K. 'Optical Imaging of Bacterial Infections' Clinical and Translational Imaging 2016, 10.1007/s40336-016-0180-0, 4/5/16

Sharp GC, Hutchinson JL, Nanette H, Freeman T, Saunders P, Norman J. 'Transcription analysis of the myometrium of labouring and non-labouring women' PLoS One 2016, vol 11, no. 5, e0155413., 10.1371/journal.pone.0155413, 13/5/16

Kieback E, Hilgenberg E, Stervbo U, Lampropoulou V, Shen P, Bunse M, Jaimes Y, Boudinot P, Radbruch A, Klemm U, Kühl AA, Liblau R, Hoevelmeyer N, Anderton SM, Uckert W, Fillatreau S. 'Thymus-derived regulatory T cells are positively selected on natural self-antigen through cognate interactions of high functional avidity' Immunity 2016, vol 44, no. 5, pp. 1114-26., 10.1016/j.immuni.2016.04.018, 17/5/16

Armstrong SD, Xia D, Bah GS, Krishna R, Ngangyung HF, LaCourse EJ, McSorley HJ, Kengne-Ouafo JA, Chounna-Ndongmo PW, Wanji S, Enyong PA, Taylor DW, Blaxter ML, Wastling JM, Tanya VN, Makepeace B. 'Stage-specific proteomes from Onchocerca ochengi, sister species of the human river blindness parasite, uncover adaptations to a nodular lifestyle' Molecular and Cellular Proteomics 2016, 10.1074/mcp.M115.055640, 25/5/16

Li Z, Vink CS, Mariani SA, Dzierzak E. 'Subregional localization and characterization of Ly6aGFP-expressing hematopoietic cells in the mouse embryonic head' Developmental Biology 2016, 10.1016/j.ydbio.2016.05.031, 25/5/16

Kitamura T, Pollard J, Vendrell Escobar M. 'Optical windows for imaging the metastatic tumour microenvironment in vivo' Trends in Biotechnology 2016, 10.1016/j.tibtech.2016.05.001, 26/5/16

Barnhill E, Hollis L, Sack I, Braun J, Hoskins PR, Pankaj P, Brown C, Beek EJV, Roberts N. 'Nonlinear multiscale regularisation in MR elastography: Towards fine feature mapping' Medical image analysis 2016, 10.1016/j.media.2016.05.012, 4/6/16

Bain C, Hawley CA, Garner H, Scott CL, Schridde A, Steers N, Mack M, Joshi A, Guilliams M, Geissmann F, Mowat AM, Jenkins S. 'Long-lived self-renewing bone marrow-derived macrophages displace embryo-derived cells to inhabit adult serous cavities' Nature Communications 2016, vol 7, ncomms11852., 10.1038/ncomms11852, 13/6/16

Grants

Translational studies in lung fibrosisGalecto Biotech ABDr Nikhil Hirani01/05/2016 - 30/04/2019£75,000.00

Analysis of hepatoctye cell cycle dynamics during liver regeneration using the Fucci2a bicistronic cell cycle reporter mouseSHERT Medical Research Scotland (SHERT)Prof Neil Henderson15/05/2016 - 09/07/2016£2,000.00

Investigation of the role of hepatic stellate cell B8 integrins in biliary fibrosisWellcome TrustProf Neil Henderson23/05/2016 - 17/07/2016£2,000.00

A national study of long term outcomes of patients admitted to Scottish intensive care units with epileptic seizuresSHERT Medical Research Scotland (SHERT)Dr Nazir Lone 30/05/2016 - 22/07/2016£2,000.00

Characterisation of mitochondrial respiratory function in primary gut tissue in mouse models of colitis and human IBDWellcome TrustDr Gwo-Tzer Ho23/05/2016 - 17/07/2016£2,000.00

The impact of the cholesterol metabolite 27-hydroxycholesterol on the pathogenesis of endometriosisSULSA Scottish Universities Life Science AllianceDr Douglas Gibson01/06/2016 - 31/07/2016£4,140.00

Any comments please contact Rebecca Aucott (raucott@exseed.ed.ac.uk)