Welcome to our two new group leaders
Two new group leaders join the Department today, Alfredo Castello and Elena Seiradake.
Dr Alfredo Castello
Dr Castello will be exploring the role of post-transcriptional networks in controlling virus infection and cell cycle progression. Dr Seiradake will develop her work on the neuronal and vascular cell guidance molecules.
Studying for his PhD in the lab of Luis Carrasco at CBMSO in Madrid first brought Dr Castello into contact with viruses. His work on viral proteins, such as proteases, demonstrated the numerous ways in which they can hijack the host gene expression machinery. This was followed by postdoctoral work as a Marie Curie Fellow at EMBL Heidelberg in the lab of Matthias Hentze where Dr Castello developed a new approach to determine the repertoire of RNA-binding proteins.
Messenger RNA (mRNA) interactome capture uses in vivo ultraviolet (UV) crosslinking of proteins to RNA, followed by oligo(dT) capture of polyadenylated RNAs and quantitative mass spectrometry, to identify the scope of RNA-binding proteins (RBPs) in living cells. Dr Castello's work led to the identification of 860 RBPs in HeLa cells, the 'HeLa mRNA interactome', adding hundreds of novel members to the previously known atlas of RBPs and revealing unanticipated links between RNA biology and cellular activities.
Recognised by the RNA community as a highly valuable tool, mRNA interactome capture has been widely cited and applied to different cell types and environmental conditions. The success led to Dr Castello's promotion to Staff Scientist in 2012, a prestigious position given to outstanding young scientists at EMBL.
His move to Oxford this autumn, made possible by an MRC Career Development Award, will allow him to build upon this success. While different reports have shown that RBPs play important roles in cell fate decision (e.g. dysfunction of specific RBPs has been associated with uncontrolled cell proliferation and cancer), the complete scope of post-transcriptional master regulators remains largely unknown. Dr Castello plans to identify RBPs playing central roles in virus infection and cell cycle progression, applying his mRNA interactome capture method as well as further developments exploiting state-of-the-art proteomics and RNA sequencing. Promising RBPs will then be subjected to a battery of in vitro and in vivo tests to gain insight into novel control mechanisms of infection and cell division.
A number of Group Leaders in the Department have interests which complement Dr Castello's research programme. Neil Brockdorff, Ilan Davis, Andre Furger and Lidia Vasilieva work on RNA metabolism, regulation and localization, whilst Nicole Zitzmann studies viral morphogenesis. Dr Castello anticipates sharing approaches with them so that both partners benefit. His interest in developing novel proteomics-based approaches to study protein-RNA interactions is also likely to bring him into contact with Shabaz Mohammed who spans the Biochemistry and Chemistry departments.
Dr Seiradake's interest in cell guidance molecules developed when she was studying for her PhD in the Cusack lab at the EMBL Grenoble Outstation. She built up this interest further as a postdoc at EMBL and subsequently upon moving to Yvonne Jones' group at STRUBI in Oxford.
Dr Elena Seiradake
During her research in Grenoble and Oxford, where she was supported on Marie Curie fellowships, she studied several guidance molecules that direct the cell along neural and vascular pathways. These include the Slits and Roundabouts, the ephrins and Eph receptors, the NetrinGs and NetrinG-ligands, and the FLRTs and Unc5s. Her work, which uses a range of structural biology, advanced light microscopy and cell biology techniques, revealed insights into how these molecules direct cell-cell communication and cell behaviour.
Dr Seiradake's move to the Department, where she will be supported by an MRC New Investigator Research grant, will allow her to focus on the Unc5 family of guidance receptors and their many signalling partners.
Unc5 receptors are involved in fundamental processes such as brain development and blood vessel formation. They guide migrating neuronal cells and their axons, and control the development of blood vessels by regulating those cells responsible for growing new vessels. Unc5 receptors also play an important role in human cancers, with most cancer cells having reduced ability to use Unc5 receptors for their guidance.
Dr Seiradake will use a multidisciplinary approach, combining X-ray crystallography, advanced microscopy and cell biology, to explore the molecular basis for Unc5 receptor function. She will study how Unc5 receptors interact with specific ligands, and how these ligands interact with further molecules, at high resolution. Together with methods that look directly at the behaviour of Unc5 on the cell surface, these studies will help understand the specific biological functions of each of the interactions.
The Department provides Dr Seiradake with excellent facilities for molecular biophysics, protein crystallisation, and super-resolution microscopy, as well as opportunities for collaboration with numerous groups studying cell surface and membrane proteins. She will continue her collaboration with Mark Sansom's group, especially postdoc Matthieu Chavent, who are experts in molecular simulation of membrane proteins. She will also be collaborating with Rainer Kaufmann, a postdoc who works jointly between Micron and Yvonne Jones' group, to carry out dSTORM, and the Eggeling group at the WIMM for STED.