The devil is in the domain: understanding protein recognition of multiple RNA targets

RNA regulation provides a finely tuned and highly co-ordinated control of gene expression. Regulation is mediated by hundreds to thousands of multi-functional RNA-binding proteins which often interact with large sets of RNAs. In this brief review, we focus on a recent work that highlights how the proteins use multiple RNA-binding domains to interact selectively with the different RNA targets. Deconvoluting the molecular complexity of the RNA regulatory network is essential to understanding cell differentiation and function, and requires accurate models for protein–RNA recognition and protein target selectivity. We discuss that the structural and molecular understanding of the key determinant of recognition, together with the availability of methods to examine protein–RNA interactions at the transcriptome level, may provide an avenue to establish these models

Project Report for the Teachers and Citizenship Knowledge Project – Seed Funded by Centre for Teachers and Teaching Research

This project report covers the purpose, experience, findings and recommendations of the seed funded Centre for Teachers and Teaching Research project examining Teachers and their Citizenship knowledge

Molecular basis of selectivity in Syncrip’s recognition of target RNAs

The highly-conserved RNA-binding protein Syncrip is an important post-transcriptional regulator of gene expression, playing a pivotal role in neuronal and muscular development during mammalian and Drosophila embryogenesis. Syncrip’s biological functions are enabled through its combinatorial usage of multiple RNA-binding domains to modulate the stability, transport and translation of a diverse, yet functionally distinct, set of RNA targets. While a number of physiological targets and targets sequences have been identified, it is still poorly understood how Syncrip selects and binds these specific RNAs at the structural and molecular level. In this thesis I ask how Syncrip is able to recognise different RNAs through the use of multiple RNA-binding modes, focusing on poly(A) RNA sequences and miR-3470 as model systems which are linked to Syncrip’s roles in the translational repression of mRNAs and the exosomal loading of miRNAs, respectively. I have found that each RNA-binding mode is characterised by different relative domain contributions to the overall specificity and affinity of either interaction. Importantly, this is underpinned by inter-domain interactions and dynamics which are associated with the formation of composite RNA-binding surfaces, as well as the definition of binding registers. Moreover, I have obtained structural information on Syncrip bound to poly(A) RNA and miR-3470, which lays the groundwork for the complete resolution of the domain arrangement in either RNA complex. The data presented here provides valuable insight into the different RNA-binding mechanisms utilised by Syncrip, which serves to expand our understanding of the molecular basis of selectivity in the protein’s recognition of target RNAs. This will hopefully guide future studies on Syncrip, particularly those that investigate its prospective role as a global repressor of translation, and the medical potential of the mechanism behind the loading of specific RNAs into exosomes

The issues in modelling freight transport at the national level

Several countries in Europe and elsewhere have a national freight transport model. This paper discusses some old and new issues for these models, based on experiences in at least seven European countries. These issues have to do with the institutional organisation of the work on model development and use, how confidence in these models can be determined and increased, the questions the national freight models are asked and their scope and level of detail. But also what the model philosophy (e.g. aggregate, disaggregate, deterministic, stochastic) should be and which influencing factors should be included. New directions are discussed, such as the trend to include more aspects of logistics decisions of firms. This increases the data requirements of the models. The potential of big data is discussed as well as approaches that use less data but more assumptions

Addressing extremism through the classroom. A research report from the Centre for Teachers & Teaching Research

The Centre for Teachers & Teaching Research explore the experiences of schools in promoting British values and helping young people resist extremist ideas and groups. A research report commissioned by the charity SINCE 9/11 on the 20th anniversary of the September 11th attacks