Dr Iwan Robert Evans
MBiochem PhD
Clinical Medicine, School of Medicine and Population Health
Senior Lecturer
+44 114 222 3695
Full contact details
Clinical Medicine, School of Medicine and Population Health
Firth Court
Western Bank
91̽»¨
S10 2TN
- Profile
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For enquiries, please contact – ClinMed-Operational@sheffield.ac.uk
After studying Biochemistry at the University of Oxford (Somerville College), I joined the MRC’s 4-year PhD program in Molecular Cell Biology at UCL’s LMCB. During my PhD I studied the generation of cell-cell repulsion downstream of the Eph receptor family of tyrosine kinases with Prof. Kate Nobes.
To study the regulation of cell migration in vivo, I subsequently joined the laboratory of Prof. Will Wood at the University of Bath. There I investigated how the migration and inflammatory responses of macrophages are controlled using the fruit fly, Drosophila melanogaster. In 2013, I was awarded a Thomas-Berry and Simpson Fellowship by the School of Medicine & Population Health at the University of 91̽»¨ to establish my own research group focusing on the role apoptotic cells play in regulation of macrophage function.
I was subsequently awarded a Sir Henry Dale Fellowship by Wellcome/The Royal Society, which I activated in 2014. Our lab uses fruit flies and a variety of cell lines (including primary human immune cells) to study regulation of the innate immune system.
- Research interests
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Lay summary
Immune cells play an important role in the normal development, general upkeep and repair of our bodies, in addition to their roles defending against infection and disease. An important function of a subset of our white blood cells (called macrophages) is to detect, ingest (phagocytose) and degrade debris, dying cells and invading pathogens.
When these processes go wrong it can cause or worsen a wide range of human diseases and conditions including autoimmunity, atherosclerosis, cancer and chronic inflammation, often due to the inappropriate behaviour of the macrophages themselves. A major problem is that we do not fully understand how the function of macrophages is controlled; understanding this would enable the generation of therapies aimed at manipulating macrophage behaviour and so prevent or reduce their contribution to these damaging conditions.
Fruit flies (Drosophila) are considerably simpler than vertebrates such as ourselves, yet the key genes important in macrophage function are also present. This makes it much easier for us to study and identify new genes involved in macrophage functions such as migration, phagocytosis and degradation of ingested material.
Importantly, fruit flies contain a population of cells called hemocytes that are very similar in their function and behaviour to our own macrophages. We study these fly macrophages to understand new mechanisms by which our own immune cells may be controlled.
Contact with cells undergoing a programmed form of death (called apoptosis), which often occurs at sites of injury or pathology, is thought to alter the behaviour of macrophages. This can be helpful in some circumstances but on other occasions it may cause macrophages to contribute to disease progression.
Drosophila hemocytes display altered responses when challenged in the presence of increased levels of cell death. One key area in our lab is to use fruit flies as a model system to understand how apoptotic cells regulate macrophage function. We are also interested in understanding how engulfment of other cargoes is controlled and regulates macrophage behaviour (e.g. pathogenic bugs).
Technical summary
Drosophila hemocytes are a population of highly migratory macrophages that disperse over the entire embryo during development. They represent the cellular arm of the innate immune system in the fly and clear both apoptotic cells and pathogens - without these functions development or survival in the face of infection are strongly perturbed, respectively.
The unparalleled imaging capabilities of hemocytes within the developing embryo, coupled with the well-established and rapid genetics of Drosophila, enable the cell biology underlying macrophage function to be determined in the context of an intact organism.
Clearance of apoptotic cells is crucial for development and this process is known to alter macrophage function. Undigested apoptotic corpses within hemocytes can suppress both their general motility and inflammatory responses. Using this model system we are studying how apoptotic corpses affect macrophage behaviour at a number of stages during the process of apoptotic cell clearance.
We are particularly focused on how the stages post-engulfment can inhibit the migratory machinery of hemocytes. This mechanism could have important consequences for a wide range of human diseases, since it could contribute to the inappropriate or prolonged localisation of macrophages at the numerous sites of pathology that contain high levels of cells dying by apoptosis.
We have established a number of collaborations with groups within the Medical School and Biomedical Science at the University of 91̽»¨ in order to translate our findings into other vertebrate systems (Zeidler, Prince and Johnston Labs).
Current Projects:
- Anti-inflammatory signalling in Drosophila macrophages.
- Impact of apoptotic cell clearance on inflammatory responses.
- Find-me cue signals in vivo.
- Blood cell proliferation and activation.
- Macrophage subtypes in health and disease.
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- . Elife, 10.
- . Cell Death & Disease, 11(8).
- . PLOS Biology, 17(5).
- . Cell, 165(7), 1658-1671.
- . Current Biology, 25(12), 1606-1612.
- . Developmental Cell, 28(4), 394-408.
- . Current Opinion in Cell Biology, 30, 1-8.
- . Curr Biol, 23, 424-429.
- . Cell Death Differ, 20, 709-720.
- . J Cell Sci, 126, 3475-3484.
- . Dis Model Mech, 4, 126-134.
- . Curr Biol, 21, R173-R174.
- . J Cell Biol, 189, 681-689.
- . J Vis Exp.
- . Curr Biol, 20, 464-470.
- . Development, 137, 1625-1633.
- . PLoS Pathog, 5, e1000518.
- . J Innate Immun, 1, 322-334.
All publications
Journal articles
- . Frontiers in Immunology, 14.
- . Elife, 10.
- . Frontiers in Cell and Developmental Biology, 9.
- . Cell Death & Disease, 11(8).
- . PLOS Biology, 17(5).
- . Journal of Cell Science, 132(5).
- . Cell, 165(7), 1658-1671.
- . PLOS Biology, 14(3).
- . Current Biology, 25(12), 1606-1612.
- . Developmental Cell, 28(4), 394-408.
- . Current Opinion in Cell Biology, 30, 1-8.
- . Curr Biol, 23, 424-429.
- . Cell Death Differ, 20, 709-720.
- . J Cell Sci, 126, 3475-3484.
- . Dis Model Mech, 4, 126-134.
- . Curr Biol, 21, R173-R174.
- Understanding in vivo blood cell migration--Drosophila hemocytes lead the way. Fly (Austin), 5, 110-114.
- Live imaging of Drosophila melanogaster embryonic hemocyte migrations.. Journal of visualized experiments : JoVE(36).
- . J Cell Biol, 189, 681-689.
- . J Vis Exp.
- . Curr Biol, 20, 464-470.
- . Development, 137, 1625-1633.
- Investigating the molecular mechanisms underlying cellular repulsion from ephrin ligands : a potential functional role for the Ena/VASP family downstream of Eph receptors..
- . PLoS Pathog, 5, e1000518.
- . J Innate Immun, 1, 322-334.
- . J Cell Sci, 120, 289-298.
- . Exp Cell Res, 310, 303-310.
- . Clinical Genetics.
Conference proceedings papers
Preprints
- Research group
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- Elliot Brooks (IICD, MRC Dimen student)
- Olivier Tardy (IICD, MRC Dimen student)
Lab Members
- Juliette Howarth, MBB masters student
- Teaching interests
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- Use of flies in biomedical research.
- Cell biology.
- Drosophila genetics.
- Macrophages in health and disease.
- Haematopoiesis.
- Professional activities and memberships
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- Member of the , University of 91̽»¨.
- Fellowships and beyond network (founder and coordinator).
- Wellbeing Champion for IICD.
- Member of the British Society for Cell Biology.
- Member of the British Society for Developmental Biology.
- Member of the Genetics Society.
- Royal Society International Exchanges Grant Panel member.
- IICD Fellows rep.
- Medical School Research Day committee member.
Links