- PhD Studentship, Queen Mary University of London (Closing date: 9th May 2018)
“Computational multi-omics for understanding the functional impact of alternative splicing in human cancer”
We are seeking an outstanding individual with a passion for devising novel computational solutions to data-rich bioscience problems, to help us make a transformational change in our understanding of the functional impact of alternative pre-mRNA splicing in human cancer. Cancer represents a significant public health problem worldwide. Large scale consortia-led “omics” studies have facilitated a better understanding of pan-cancer genomes, transcriptomes, and proteomes. However, studies integrating pan-cancer omics datasets have been lacking, and this has limited how, for example, misregulation of transcriptomes impacts on proteomic diversity and influences human cancer phenotypes. Alternative pre-mRNA splicing (AS) is a ubiquitous genetic process that results in the “shuffling” of coding and non-coding information in the genome, creating proteomic diversity. Recently, global misregulation of AS has been associated with cancer phenotypes due to changes both within tumour cells and the microenvironment, but little is known of the global impact on pan-cancer proteomes. The aim of this project is to devise, implement and apply novel proteomics informed by transcriptomics (PIT) methodology to integrate human pan-cancer transcriptomics and proteomics data. The project will be supervised by Conrad Bessant (Professor of Bioinformatics, School of Biological and Chemical Sciences) and Dr Prabhakar Rajan (Clinical Senior Lecturer in Urology, Barts Cancer Institute and Consultant Urologist, Barts Health NHS Trust). The project will provide the student with a unique opportunity to gain valuable computational and translational research training, and will yield novel insights into cancer biology, biomarkers and therapies. For further details, please see:
2. Postdoctoral fellow: Regulation of RNA metabolism in lung epithelium by HuR. Astra Zeneca
We’re currently looking for talented scientists to join our innovative academic-style Postdoc. From our centre in Gothenburg, SE, you’ll be in a global pharmaceutical environment, contributing to live projects right from the start. You’ll take part in a comprehensive training programme, including a focus on drug discovery and development, given access to our existing Postdoctoral research, and encouraged to pursue your own independent research in cutting edge laboratories. It’s a newly expanding programme spanning a range of therapeutic areas across a wide range of disciplines.
What’s more, you’ll have the support of a leading academic advisor, who’ll provide you with the guidance and knowledge you need to develop your career. This is an exciting area that hasn’t been explored to its full potential, making this an opportunity to make a real difference to the future of medical science.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines for some of the world’s most serious diseases. But we’re more than one of the world’s leading pharmaceutical companies. At AstraZeneca, we’re proud to have a unique workplace culture that inspires innovation and collaboration. Here, employees are empowered to express diverse perspectives – and are made to feel valued, energised and rewarded for their ideas and creativity.
Our Respiratory, Inflammation and Autoimmunity team offers definitive expertise to colleagues across the business. You’ll help respiratory patients in areas with medical needs that aren’t being fully met, including chronic obstructive pulmonary disease and asthma and rheumatic disorders tackling these diseases from three areas lung immunity, lung epithelium, and lung remodelling/regeneration. Right now, We are a leading figure in inhaled drug development, and our new Inhalation Centre in Gothenburg, Sweden coupled with our work in new modalities is set to extend that lead even further.
A Postdoctoral position is available at Respiratory, Inflammation and Autoimmunity Innovative Medicines Unit, AstraZeneca R&D, Gothenburg, Sweden, in the Lung Epithelium department. The successful candidate will work in a cross-disciplinary research team that integrates basic, translational and clinical science, with epithelial barrier function and epithelial senescence as key focus areas. This project will employ a broad range of molecular and cellular biological methods to understand different levels of RNA regulation occurring in response to environmental stress associated with respiratory diseases. The selected candidate will have access to state-of-the-art capabilities and new modalities to target specific RNA-protein interactions, the project offers a unique opportunity to establish RNA metabolism as a novel target landscape in respiratory diseases.
3. Researcher, Post-doctoral level (15 months)
Research Unit : UMR 8227: Laboratory of Integrative biology of Marine Models
Location: Station Biologique de Roscoff (on the north coast of Brittany, FRANCE)
Function: Structural investigation of RNA : protein interactions
Salary: 2900 €/month (approx.). The grant (SAD) is issued by The Region of Brittany.
The candidate must have worked 12 months (at least) between June 2014 and May 2017 outside France. The team « Translation, Cell Cycle and Development » investigates the regulation of translation initiation at the early stages of development, mainly in the sea urchin model. We aim to highlight the impact of RNA structural elements on the control of when and where the translation of a specific mRNA is initiated. The role of the future recruit will be to foster the structural approaches required to fully understand the mechanisms by which a messenger RNA is driven to be translated into a protein.
At the core of the translation process is the messenger RNA (mRNA), which beyond its function of code to be translated into a protein, comprises structural elements of variable stability. These are essentially located in the untranslated regions (5’UTR and 3’UTR) and participate to the control of translation. The general mechanism of mRNA activation and loading on the active ribosomes goes through the recognition of the cap structure at the 5’-end, assembly of the preinitiation complex and scanning of the RNA to find the initiation codon (1). This may be influenced by signature sequences, such as the 5’ oligopyrimidine (5’TOP) motif, bound by the protein LARP1 to control ribosome biogenesis (2). Another mechanism consists of directly loading the ribosome in the vicinity of the initiation codon. This is the case of viral messengers, where recruitment of the ribosome is achieved thanks to special IRES (Internal Ribosome Entry Site) structures of the RNA (3). Functional IRESs have also been demonstrated in non-infected cells, but only few examples of structural elements (loops, double-stranded regions) of the RNA were given thus far (4), suggesting the participation of RNA-chaperone or RNA-binding proteins in the mechanism (5). Other structures of the mRNA have been shown to be involved in defining where translation takes place, or to coordinate synchronous translation of several mRNAs. This is the case of a stem-loop found in the 5’-UTR of the collagen alpha-1 and alpha-2 mRNAs, which ensures proper stoichiometry of the
collagen fiber. It involves the LARP6 protein, which binds the stem-loop and prevents ribosome loading on the initiation codon. Interestingly, the stem-loop and LARP6 are also involved in focusing the translation of collagen at discrete foci of the endoplasmic reticulum (6). These few examples underline that there are many RNA recognition events by which specific (e.g. LARPs) or less specific RNA-binding proteins (such as translation factors) contribute to the assembly of the initiation machinery. The Translation, Cell Cycle and Development team wishes to complete current traditional biochemical investigations of complex formation to include structural approaches such as
crystallography and SAXS to understand mechanisms of assembly at stake in translation initiation. To lay the foundation for structural work and as a first insight into the type of complexes that assemble on the 5’UTR of mRNAs we propose to tackle complexes involving proteins of the LARP family. Until now, as we have shown in LARP7 (7), the LA-module was known to use its two domains LAM and RRM in a side-by-side configuration to clamp the end of an RNA chain. The LAmodule of LARP6 binds the RNA in a different way (8). It involves the interdomain linker to constrain the configuration of LAM and RRM to generate a specific surface to recognize the hairpin structure. In order to establish how this works, and in collaboration with Pr Maria Conte (King’s College,
London), a crystallographic study of the LARP6 complex with the collagen stem-loop will be attempted in parallel with SAXS investigations. Future research within the structural project will include the new complexes discovered during our investigations on cellular IRESs involved in translation initiation after fertilization in the sea urchins.
The work is at the boundary between biochemistry and structural expertise. Proficiency in RNA biochemistry is required but candidates with basic knowledge of RNA will be considered if their field of expertise in structural investigations (crystallography, SAXS) includes analyses of complexes.
Dr. Anne-Catherine Dock-Bregeon: firstname.lastname@example.org
+33 (0)298 292 332
Station Biologique de Roscoff Place Georges Teissier 29680 ROSCOFF FRANCE
4. Postdoc Position in Epitranscriptomics (m6A mRNA methylation)
We are looking for a highly motivated Postdoc with a deep interest in epitranscriptomics to join our molecular genetics Drosophila research group in the School of Biosciences, University of Birmingham, UK to follow up on our findings published recently in Nature (Haussmann et al, 2016).
Our laboratory is interested in resolving the function of m6A mRNA methylation in the regulation gene expression. We are applying a combination of state of the art genetic and molecular tools in a Drosophila genetic model complemented by in vitro molecular biology assays to understand how methylation sites are selected and how methylation levels are determined.
Applicants must hold a PhD degree in biology and have extensive experience in molecular biology. Previous experience in Drosophila genetics or other genetic model systems would be appreciated.
This BBSRC funded fixed-‐term appointment is available for 36 months starting in 2018. Starting salary is in the range of £28,982 to £40,082.
To apply, please go to http://www.jobs.ac.uk/job/BGH859/research-‐fellow
(Ref 58446) before 7. January 2017. Applications should include a full CV, a one page personal statement and contact details for at least two referees.
For informal enquiries please contact Dr Matthias Soller (email@example.com
4. Tenure track RNA chemist.
The Department of Chemistry at the University of Massachusetts (http://www.chem.umass.edu) and the Center for Bioactive Delivery at the Institute for Applied Life Sciences (IALS, https://www.umass.edu/cbd/) are embarking on a strategic hiring program enabled by the creation of this Institute. Applications are invited for a full-time, tenure track faculty position in the Chemistry Department at the Assistant Professor level to begin September 2018 or thereafter. We would also consider candidates at other levels, commensurate with experience. We seek applicants who will develop or continue a vigorous research program in the use of or delivery of biomolecules, particularly RNA and proteins for the development of therapeutic candidates to treat diseases or disorders. Areas of interest include, but are not limited to, siRNA/miRNA methodologies or delivery technologies, mRNA-based therapies, RNA/protein design, selection or engineering, and novel genome editing technologies. The full details of this position can be found at: