Key details
Uncovering the role of RNA in motor neuron disease
Amyotrophic lateral sclerosis (ALS), the most common type of motor neuron disease (MND), is a fatal condition that causes progressive weakness of the muscles due to the degeneration of motor neurones in the brain and spinal cord. Although there are some treatments available to slow progression, greater understanding of the underlying causes is needed to develop more effective treatments and to help those affected live longer, healthier lives.
The Ule Lab is focused on a versatile molecule called ribonucleic acid (RNA), which has many roles in cells. RNA interacts with proteins to form large complexes, and evidence suggests that changes in these interactions can lead to the characteristic toxic aggregates seen in neurodegenerative diseases such as ALS and frontotemporal dementia. By developing and applying innovative new biochemical and computational techniques, Jernej’s team aim to find out why this occurs and how to stop it using new therapeutics.
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Prof Jernej Ule
Prof Jernej Ule is a Group Leader and Centre Director at the UK DRI at King's. Find out more about his career and expertise on his profile page.
Research summary
Researchers are discovering an increasing number of roles for RNA in the cell.
Credit: Shutterstock/No beast so fierce
RNA networks in ALS/FTD
Ribonucleoprotein complexes (RNPs) form when proteins bind to an RNA molecule, helping guide the RNA on its journey through the cell, while the RNAs also regulate the functions of bound proteins. These complexes have many regulatory roles in development, and their defects can lead to various diseases. Mutations in RNA-binding proteins (RBPs) or non-coding RNAs alter important RNPs to cause neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Moreover, accumulations of RNP aggregates are a pathological hallmark of these diseases.
Prof Ule aims to unravel mechanisms that promote healthy dynamics of RNPs to prevent them from aggregating and how this is established through interactions between RNAs and proteins. The Ule Lab also study the roles of disordered regions that are commonly present in RBPs, which contribute to the assembly and dynamics of RNPs, as well as their aggregation. The team have built a framework of systems biology techniques such as iCLIP (individual-nucleotide resolution UV crosslinking and immunoprecipitation of protein-RNA complexes), which integrate biochemistry and computational biology to obtain a comprehensive map of interactions between proteins and their RNA partners within cells. Thereby they can characterise the roles of RNPs in cellular transitions in development and disease.
Main objectives and research goals:
In the UK DRI research programme, the Ule Lab aim to examine the fundamental principles guiding the assembly and dynamics of RNPs that play central roles in FTD/ALS.
- Employing a systems biology toolbox to study the impact of disease-causing mutations on RNP assembly. Most mutations locate to the poorly-understood disordered regions of proteins, and the researchers study their roles in the condensation of RNPs.
- To study homeostatic pathways that maintain protein-RNA condensates in a healthy functional range and prevent their aggregation and how alterations in these pathways affect neurodegeneration.
- To develop new molecular sensors and therapeutic approaches that modulate the homeostatic pathways.
Key publications
Vacancies
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Key details
- Location UK DRI at King's
- Salary: £45, 031 - £52,514 per annum
- Lab: Prof Jernej Ule
The UK Dementia Research Institute (UK DRI) is the biggest UK initiative supporting research to fill the major knowledge gap in our basic understanding of the diseases that cause dementia.
About the role:
Professors Jernej Ule and Benjamin Blencowe are seeking a Research Associate to join a team of researchers working on the Wellcome funded project.
The successful candidate will focus on the design and testing of auto-gating therapeutics in the iNeuron models of neurologic diseases, which will also involve the generation and culture of induced pluripotent stem cell (iPSC) lines, their differentiation into neurons and analyses with transcriptomics and imaging, thus contributing to relevant publications in collaboration with other team members.
Some of the key skills involved include:
- Planning and performing high quality research under co-supervision of Ben Blencowe and Jernej Ule and in collaboration with other team members.
- Preparing figures, summarising the results and playing a leading role in writing the manuscripts to be submitted to peer-review journals.
- Supervision of visiting and rotating students related to the post holder’s work.
- Contributing to the multidisciplinary research strategy of the Centre and department
- Attend, contribute and present at international conferences as well as internal meetings at UK DRI, Departmental and with external collaborators as appropriate.
- Regular interaction with collaborators and coordination of joint work.
- Ensuring the highest standard of record keeping, maintaining accurate, complete, and up to date records.
- Continue professional development, including participation in staff development and review procedures in accordance with King’s guidelines, including annual formal appraisal.
About You:
Essential criteria
- Hold a PhD in Molecular or Cellular Biology, or a closely related discipline.
- Experience with molecular biology of ribonucleoprotein complexes and RNA regulation
- Experience in genome editing techniques.
- Experience with high-throughput sequencing and its analysis.
- Experience in immunostaining, microscopy and image analysis.
- Ability to work independently, manage competing priorities, and take initiative in problem-solving and experimental troubleshooting.
- Excellent communication skills
- Excellent organizational skills
**** ***Please note that this is a PhD level role but candidates who have submitted their thesis and are awaiting award of their PhDs will be considered. In these circumstances the appointment will be made at Grade 5, spine point 30 with the title of Research Assistant. Upon confirmation of the award of the PhD, the job title will become Research Associate and the salary will increase to Grade 6.
Desirable criteria
- Experience with working with iPSC cells
- Experience with Transcriptomics
- Experience with the studies of protein-RNA condensates
Lab members
Collaborators
Lab funders
Thank you to all those who support the Ule Lab!
