南安普敦大学招收化学博士
Project description
We are seeking a highly motivated individual to join our team as a fully funded PhD student developing new chemical modifications to improve the potency of splice-switching oligonucleotides.
Splice-switching oligonucleotides (SSOs) have recently emerged as powerful precision medicines for life-threatening diseases. Unlike conventional drugs which act on proteins, SSOs bind to and re-direct mRNA processing, altering the production of disease-associated proteins. SSOs can be designed for individual patients based on their genome and can be developed in a much shorter time frame than other classes of drugs. This was proven in 2018 when the FDA approved the SSO drug Milasen for Batten disease.1 Milasen was the first ever personalised medicine designed for a single patient and was developed in ten months, setting a ground-breaking precedence that could revolutionise how genetic diseases are treated.
The aim of this project is to develop a new class of SSO analogues designed to overcome existing limitations, reduce the required dose, and decrease the likelihood of toxic side effects. Innovation in nucleic acid chemistry has been integral to the success of SSOs in the clinic. Chemical modifications protect the SSOs from rapid digestion in vivo as well as enhance their interaction with RNA. Despite this, SSOs have yet to reach their full potential due to challenges associated with efficacy, delivery, and toxicity. We will develop new synthetic routes to prepare the SSO analogues, perform biophysical studies to investigate how well the new compounds interact with target RNA, and evaluate their biological activity in cell-based assays using clinically relevant disease models.
We are looking for a student who enjoys organic synthesis and is keen to work in the rapidly emerging field of nucleic acid therapeutics. This is an interdisciplinary project, and the student will receive training in a range of organic and chemical biology techniques. This is likely to include synthetic organic chemistry, solid-phase oligonucleotide and peptide synthesis, biophysical and biochemical techniques, and biological assays in cell culture. The student will also have the option to attend relevant international conferences and training events.
Entry Requirements
A very good undergraduate degree (at least a UK 2:1 honours degree, or its international equivalent).
Closing date: applications should be received no later than 31 August 2023 for standard admissions, but later applications may be considered depending on the funds remaining in place. Applications will be considered in the order that they are received, and the position will be considered filled when a suitable candidate has been identified. The first round of interviews is likely to be in the first week of April.
Funding: For UK students, Tuition Fees and a stipend of £17,668 tax-free per annum for up to 3.5 years.
For further information please contact: feps-pgr-apply@soton.ac.uk
If you wish to discuss any details of the project informally, please contact Dr Ysobel Baker, Email: y.r.baker @ soton.ac.uk
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