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Research Associate

3 months ago

Hammersmith, United Kingdom Imperial College London Full time

We are looking for two highly motivated and driven researchers with a PhD or equivalent and a strong background in molecular and/or cellular biology to join the research group led by Dr Aida Martinez-Sanchez within the section of Cell Biology and Functional Genomics at Imperial College London (ICL). Our lab is based at the Imperial Centre for Translational and Experimental Medicine (ICTEM) in the Hammersmith Hospital campus.

The first post is funded by the Medical Research Council (MRC) to investigate the mechanism of action of miR-125b in β-cells and its targeting potential in diabetes (36 months duration).

The second post is funded by the Diabetes UK to investigate the role of cation-dependent mannose-6-phosphate receptor (M6PR) in β-cells and its potential as therapeutic target for the treatment of diabetes (39 months duration).

Our research programme focuses on understanding the role that microRNAs and their gene targets play in controlling β-cell function and in finding new ways to target these pathways to improve the treatment of diabetes. Both projects will be performed in close collaboration with other research teams within and outside ICL.

Our laboratory is committed to mentoring scientists and nurturing creative thinking and scientific independence. These positions will not only provide the opportunity to develop, cutting-edge research skills but also highly transferable skills such as communication, leadership and management. ICL provides exceptional support to postdoctoral researchers, including the access to a wide variety of training opportunities and individual support.

We are looking to hire postdoctoral researchers that are interested in exploring β-cell biology and in deciphering the molecular and cellular mechanisms underlying the regulatory axis hyperglycaemia-AMPK-miR-125b-M6PR.

For the first post, you will generate mice with miR-125b loss-of-function in pancreatic β-cells using genetic tools and modified antisense oligos, whilst viral vectors will be used to reduce miR-125b function in human islets. You will perform _in vivo_ experiments to assess glucose homeostasis in the mouse models and isolated pancreatic islets will be thoroughly characterised using a wide array of techniques, including high-resolution microscopy, molecular sensors and FRET. The role of miR-125b in lysosomal and mitochondrial function and its contribution to glucose/AMPK-mediated regulation of these processes will be interrogated in detail in these models but also using CRISPR/Cas9 and lentiviral vectors in islets and cell lines.

For the second post, you will generate mice with M6PR loss-of-function in pancreatic β-cells and perform _in vivo _experiments to characterise glucose homeostasis. Isolated pancreatic islets will be functionally characterized in depth using a wide array of techniques that will also include the use of molecular sensors, FRET and microscopy. Special attention will be paid to lysosomal function and related processes including autophagy and trafficking and degradation of transmembrane receptors, including GLP-1R and other GPCRs expressed in β-cells. You will also combine cell culture and the use of mice fed different diets to determine whether hyperglycaemia controls M6PR expression in an AMPK-miR-125b manner. You will also use a novel approach involving CRISPR/Cas and adeno-associated virus to prevent miR-125b-mediated repression of M6PR specifically in β-cells _in vivo_.

**Duties and responsibilities**:
The post holders will lead the projects described above and take the initiative in the planning of research, while identifying and developing suitable techniques and apparatus for the collection and analysis of data. They will ensure the validity and reliability of data, maintain accurate and complete records of findings and write reports for submission to research sponsors**. **They will also participate in the training and supervision of junior members of the team.

**Essential requirements**:

- **Research Associate**: Hold or be about to obtain a PhD in cellular and molecular biology or a closely related discipline, or equivalent research, industrial or commercial experience
- ** Research Assistant**: Near completion of a PhD in cellular and molecular biology or a closely related discipline, or equivalent research, industrial or commercial experience- Practical experience within a research environment and/or publication in relevant and refereed journals are essential.
- The post holder will be required to work with mínimal supervision to meet deadlines.
- Excellent written and verbal communication skills are required.
- Willingness to work as part of a team and to contribute to the supervision of other researchers at different levels is also essential.

It is also essential to have knowledge and practical research experience on some of the following:

- Cell culture and molecular, cellular and biochemical approaches
- Lysosomal and/or mitochondria biology
- β-cell biol