Dr Iwan Robert Evans MBiochem PhD
Sir Henry Dale Fellow
Department of Infection Immunity & Cardiovascular Disease
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, as a model system. In 2013 I was awarded a Thomas-Berry and Simpson Fellowship by the Medical School at the University of Sheffield to establish my own research group focusing on the role apoptotic cells play in regulation of macrophage function. I was awarded a Sir Henry Dale Fellowship by the Wellcome Trust/Royal Society, which I activated in 2014.
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.
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. Therefore we are using this system to try to understand how apoptotic cells regulate macrophage function.
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 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.
Use of flies in biomedical research, cell biology, Drosophila genetics.
- Sir Henry Dale Fellow.
- Member of the Bateson Centre, University of Sheffield.
- Personal website: http://iwanrevans.weebly.com.
- Member of the British Society for Cell Biology.
- Member of the British Society for Developmental Biology.
- Anti-inflammatory signalling in Drosophila macrophages.
- Impact of apoptotic cell clearance on inflammatory responses.
- JAK/STAT signalling in Drosophila blood cells.
For key publications see below. For a full list of publications click here.
- Weavers H, Evans IR, Martin P & Wood W (2016) Corpse Engulfment Generates a Molecular Memory that Primes the Macrophage Inflammatory Response. Cell, 165(7), 1658-1671. View this article in WRRO
- Evans IR, Rodrigues FSLM, Armitage EL & Wood W (2015) Draper/CED-1 Mediates an Ancient Damage Response to Control Inflammatory Blood Cell Migration In Vivo. Current Biology, 25(12), 1606-1612. View this article in WRRO
- Bilancia CG, Winkelman JD, Tsygankov D, Nowotarski SH, Sees JA, Comber K, Evans I, Lakhani V, Wood W, Elston TC, Kovar DR & Peifer M (2014) Enabled Negatively Regulates Diaphanous-Driven Actin Dynamics In Vitro and In Vivo. Developmental Cell, 28(4), 394-408. View this article in WRRO
- Evans IR & Wood W (2014) Drosophila blood cell chemotaxis. Current Opinion in Cell Biology, 30, 1-8. View this article in WRRO
- Razzell W, Evans IR, Martin P & Wood W (2013) Calcium flashes orchestrate the wound inflammatory response through DUOX activation and hydrogen peroxide release. Curr Biol, 23, 424-429. View this article in WRRO
- Evans IR, Ghai PA, Urbancic V, Tan KL & Wood W (2013) SCAR/WAVE-mediated processing of engulfed apoptotic corpses is essential for effective macrophage migration in Drosophila. Cell Death Differ, 20, 709-720. View this article in WRRO
- Comber K, Huelsmann S, Evans I, Sanchez-Sanchez BJ, Chalmers A, Reuter R, Wood W & Martin-Bermudo MD (2013) A dual role for the betaPS integrin myospheroid in mediating Drosophila embryonic macrophage migration. J Cell Sci, 126, 3475-3484.
- Tucker PK, Evans IR & Wood W (2011) Ena drives invasive macrophage migration in Drosophila embryos. Dis Model Mech, 4, 126-134.
- Evans IR & Wood W (2011) Drosophila embryonic hemocytes. Curr Biol, 21, R173-R174.
- Evans IR, Hu N, Skaer H & Wood W (2010) Interdependence of macrophage migration and ventral nerve cord development in Drosophila embryos. Development, 137, 1625-1633.
- Stramer B, Moreira S, Millard T, Evans I, Huang CY, Sabet O, Milner M, Dunn G, Martin P & Wood W (2010) Clasp-mediated microtubule bundling regulates persistent motility and contact repulsion in Drosophila macrophages in vivo. J Cell Biol, 189, 681-689. View this article in WRRO
- Moreira S, Stramer B, Evans I, Wood W & Martin P (2010) Prioritization of competing damage and developmental signals by migrating macrophages in the Drosophila embryo. Curr Biol, 20, 464-470.
- Evans IR, Zanet J, Wood W & Stramer BM (2010) Live imaging of Drosophila melanogaster embryonic hemocyte migrations. J Vis Exp. View this article in WRRO
- Vlisidou I, Dowling AJ, Evans IR, Waterfield N, ffrench-Constant RH & Wood W (2009) Drosophila embryos as model systems for monitoring bacterial infection in real time. PLoS Pathog, 5, e1000518. View this article in WRRO
- Defaye A, Evans I, Crozatier M, Wood W, Lemaitre B & Leulier F (2009) Genetic ablation of Drosophila phagocytes reveals their contribution to both development and resistance to bacterial infection. J Innate Immun, 1, 322-334.