iCASE scholarship (PhD/DPhil) to elucidate how the brain develops

This scholarship will allow you to work in a multidisciplinary team between Prof. Ilan Davis (Microscopy and brain development), Alfredo Castello (RNA biology and viruses) and Martin Booth (Industrial partner Aurox.ltd).

Combining these expertise, we will build an affordable very fast confocal microscope with a small footprint, dedicated to prolonged live cell imaging of explanted brains in 3D, as well as to rapid 3D imaging of multiple single RNA molecules. Once built the microscope will have many applications. Depending on the background of the student, the work will involve a balance of optical engineering / biological experiments / data analysis. The student will have access to world leading training and collaborations through Micron Oxford to all the relevant expertise required for these three disciplines.

Discovering the cellular RNA-binding proteins controlling virus infection

Our new research published in Molecular Cell has uncovered that virus infection rewires cellular RNA-binding proteins (RBPs) on a global level. This reflects two antagonistic processes: the virus hijacking key cellular resources and the antiviral defence mechanisms of the cell. We discovered dozens of RBPs that play central roles in virus infection and opens new avenues for the development of antiviral therapies. Find out more about this work here.

Original article

System-wide profiling of RNA-binding proteins uncovers key regulators of virus infection. Garcia-Moreno M*,  Noerenberg M*, Ni S*,  Järvelin AI, González-Almela E, Lenz CE, Bach-Pages M, Cox V, Avolio R, Davis T, Hester S, Sohier TJM, Li B, Heikel G, Michlewski G,  Sanz MA, Carrasco L, Ricci EP, Pelechano V, Davis I, Fischer B, Mohammed S and Castello A. Molecular Cell. DOI: https://doi.org/10.1016/j.molcel.2019.01.017

Riboregulation: when RNA controls protein function

It is established that interactions of proteins with RNA play a crucial role at regulating RNA fate. However, a recent work led by the Hentze lab at EMBL has discovered that the reverse relationship is also possible. In other words, proteins can be regulated by RNA. We refer to this phenomenon as ‘riboregulation’.

This study shows that the RNA vault 1-1 (vtRNA1-1) interacts and regulates the protein p62, which is a key component of the autophagy machinery. As its name suggests, autophagy is a process by which a cell ‘eats itself’ to recycle its unnecessary or dysfunctional components. Interaction of vtRNA1-1 with p62 inhibits autophagy and this regulatory circuit exists in both human and mouse cells.

Importantly, the amount of vtRNA1-1 inside a cell varies according to the cell’s nutritional status. When is deprived of amino acids, vtRNA1-1 is reduced to enhance autophagy that will refill the pool of amino acids from unnecessary proteins to cover the cell needs.

This study raises the question of how common ‘riboregulation’ is and which processes are controlled by RNA. We hope to find the answer to these important questions in the years to come.

Original publication

The Small Non-coding Vault RNA1-1 Acts as a Riboregulator of Autophagy. Horos R, Büscher M, Kleinendorst R, Alleaume AM, Tarafder AK, Schwarzl T, Dziuba D, Tischer C, Zielonka EM, Adak A, Castello A, Huber W, Sachse C, Hentze MW. Cell. 2019 Feb 21;176(5):1054-1067.e12. doi: 10.1016/j.cell.2019.01.030. Epub 2019 Feb 14.PMID: 30773316