斯特拉斯克莱德大学PhD Position in Exploration of Next-Generation Hydroxyl Group Bioisosteres申请条件要求-申请方
主办方
思克莱德大学
PhD直招介绍
About the Project
Summary
5-Hydroxymethylcytidine (5hmC) is a promising nucleobase modification for use in therapeutic oligonucleotides and self-amplifying RNA vaccines. However, 5hmC is metabolically unstable and analogues of this modification are needed for medical applications. This studentship will develop synthetic routes that replace the 5hmC hydroxyl group with bioisosteres and then incorporate these building blocks into oligonucleotides and longer RNA molecules. The project will then explore the impact of these modifications using a range of biophysical techniques, and biologically evaluate the suitability of these new modifications for use in therapeutic oligonucleotides and RNA vaccines.
Project details
5-Hydroxymethylcytidine (5hmC) has recently emerged as a transformative nucleobase modification for self-amplifying RNA (saRNA) vaccines, delivering 14-fold higher transfection efficiency than other modifications (e.g. pseudouridine-mRNA) while reducing innate immune responses. However, the use of 5hmC for RNA therapeutic applications is limited by metabolic instability as it is susceptible to enzymatic oxidation.
This studentship proposes to overcome these limitations through the development of synthetic routes to replace the 5hmC hydroxyl group with metabolically stable analogues. With these synthetic routes established, phosphoramidites and triphosphates of these cytidine analogues will be prepared for incorporation into RNA by solid phase and enzymatic synthesis, respectively. Finally, the biophysical and biological properties of these cytidine analogues when incorporated into oligonucleotides and longer RNA molecules will be explored in vitro and in live cell assays. A successful outcome of this studentship would be access to a new generation of nucleotide modifications suitable for further therapeutic development in RNA vaccines or as a key building block in oligonucleotide therapeutics.
Training
The student undertaking this project will receive unparalleled training in medicinal chemistry and nucleic acid chemical biology. The Burley group has extensive experience in small molecule and nucleoside synthesis, solid phase peptide/nucleic acid synthesis, biophysical analysis and structural biology. The group has state-of-the-art automated synthesizers, HPLC equipment for purification and analysis, and mass spectrometry facilities. Biological evaluation will be done in collaboration with Haiyan Zhou (UCL) and Yvonne Perrie (Strathclyde). The successful applicant will also be expected to spend at least 3 months working alongside chemical biology groups at GSK’s Stevenage site.
References
(1) McGee, J. E. et al. Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency. Nature Biotechnology 2025, 43 (5), 720–726.
(2) Peschke, F. et al. Reactivity Profiling for High-Yielding Ynamine-Tagged Oligonucleotide Click Chemistry Bioconjugations. Bioconjugate Chemistry 2024, 35 (11), 1788–1796.
思克莱德大学 PhD Position in Exploration of Next-Generation Hydroxyl Group Bioisosteres项目有没有奖学金，是不是全奖Phd招生，下面我们一起看一下【大学名称】Phd的奖学金资助情况
项目资助情况
Funding Notes
Fully funded 4-year (48-month) PhD studentship. One place is available.
This is an EPSRC Industrial Doctoral Landscape Award (IDLA) studentship in collaboration with GlaxoSmithKline (GSK). The studentship is open to both home and international students and includes tuition fees and an annual stipend for 4 years. The stipend is at the standard UKRI rate.
Full-time study only.
思克莱德大学Phd申请条件和要求都有哪些？PhD Position in Exploration of Next-Generation Hydroxyl Group Bioisosteres项目是不是全奖？有没有奖学金？下面我们一起看一下思克莱德大学申请Phd直招需要具备哪些条件和要求，以及托福、雅思语言成绩要到多少才能申请。
申请要求
Eligibility
Candidates must have a strong background in Synthetic Organic or Medicinal/Biological Chemistry and have obtained a first-class or upper second-class (2:1) UK Honours degree, or overseas equivalent. If English is not your first language, you must have an IELTS score of at least 6.5 with no component below 5.5. The studentship is open to applicants of Home (Scottish), Rest of UK and International fee status.
Keywords
5-hydroxymethylcytidine; mRNA vaccines; oligonucleotide therapeutics; nucleoside chemistry; phosphoramidite
报名方式
招生人信息
Prof G Burley
邮箱：glenn.burley@strath.ac.uk
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