约克大学PhD position in Polymerases for the synthesis of functionalised oligonucleotides申请条件要求-申请方
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约克大学
PhD直招介绍
About the Project
Background
Outside the cellular roles of nucleic acids as DNA and RNA, synthetic nucleic acids with chemical modifications have the potential to be exploited in diverse ways from DNAzymes to means of long-term data storage. Such functionalised oligonucleotides have already entered into the biomedical space in the form of therapeutics and gene delivery vehicles. To date, solid-phase phosphoramidite chemistry remains the only route to synthesise oligonucleotides. A major caveat of this approach lies in its poor atom efficiency clubbed with the extremely high organic solvent usage (over 4000kg per kg of a short oligomer made) that has brought into focus attempts to improve the sustainability of the process of oligonucleotide synthesis. Recent advances in utilising enzymes for the synthesis of oligonucleotides have shown the feasibility and relevance of this approach but also indicate that no enzyme can provide a “one-size-fits-all” solution. You will develop a toolkit of designer polymerases that will be used to devise an “enzymes-only” aqueous approach to selectively incorporate various nucleotide chemistries. The ultimate goal will be to demonstrate their use to make therapeutic oligonucleotides.
Objectives
Design and screen for thermostable polymerase variants capable of utilising new nucleotide modifications
Biochemical and kinetic characterisation of the novel template-independent X-family polymerase(s)
Structure determination using X-ray crystallography
Establish a polymerase-dependent method to synthesise therapeutically relevant oligonucleotides
Experimental Approach
The project will encompass a broad range of techniques well-established within the Mukherjee and Grogan groups and you will benefit from this existing expertise. Our group has identified a fungal X-family polymerase with the intrinsic property of accepting a variety of nucleotides modified at the ribose sugar and backbone in the absence of templating information (unpublished). We will begin with this polymerase as a scaffold to build more thermostable enzymes integrated with desired template-independent incorporation properties. These polymerases will be evaluated for their stability and substrate binding affinities using a combination of biochemical and biophysical approaches not limited to gel-based and liquid chromatography coupled mass spectrometry (LC-MS) to characterise the reactions and determine kinetic chemical reaction rates (ensemble transient state kinetics and single-molecule fluorescence correlation spectroscopy). You will use protein X-ray crystallography to obtain high-resolution structural information to understand the mode of non-cognate substrate incorporation. Finally, the optimised enzyme toolkit will be tested to achieve the goal of synthesising oligonucleotide therapeutics.
Novelty The field of chemoenzymatic approaches towards oligonucleotide synthesis is in its infancy with immense potential for impactful discoveries and applications. All advances in devising new enzymatic routes to synthesis will be beneficial to industry and long-term to biomedical applications.
Scientific Training This project will provide you with a highly cross-disciplinary training in a wide range of skills including protein-nucleic acids biochemistry (purification and enzyme kinetics), analytical chemistry (LC-MS)( https://www.york.ac.uk/mass-spectrometry/ ), biophysics (single molecule FRET, fluorescence correlation spectroscopy)( https://excitinginstruments.com/ ) and structural biology (X-ray crystallography) that will be transferable to industry and beneficial for a future career in biomedical sciences. Both the groups of Dr. Purba Mukherjee( https://sites.google.com/view/mukherjeelab/home ) and Prof. Gideon Grogan( https://www.york.ac.uk/chemistry/people/ggrogan/ ) are part of the York Structural Biology Laboratory (YSBL)( https://www.york.ac.uk/chemistry/research/ysbl/ ) which will allow you to integrate within the framework of a larger array of cutting-edge research in various aspects of chemical and structural biology. Members of the Mukherjee and Grogan groups will provide training for the various methodologies important for the project. Additional training as needed will be arranged through the various facilities and through visits to collaborators.
What makes a suitable candidate? The project is a good fit for a student interested in tackling a challenging problem at the interface of chemistry and biology. Students from diverse backgrounds with an enthusiastic and innovative problem-solving attitude are encouraged to apply. You will have the opportunity to be in an interdisciplinary, collaborative environment at York with expertise in the design of new, biotechnologically relevant enzymes.
You will follow our core cohort-based training programme to support the development of scientific, transferable and employability skills, as well as training on specific techniques and equipment. Training includes employability and professionalism, graduate teaching assistant training and guidance on writing papers.
https://www.york.ac.uk/chemistry/study/postgraduate-research/training-and-careers/
There will be opportunities for networking and sharing your work both within and beyond the University. Funding is provided to enable you to attend conferences and external training. The department also runs a varied and comprehensive seminar programme.
Equality and Diversity
The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. The Department strives to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel: https://www.york.ac.uk/chemistry/ed/ .
As part of our commitment to Equality and Diversity, and Widening Participation, we are working with the YCEDE project ( https://ycede.ac.uk/ ) to improve the number of under-represented groups participating in doctoral study. All Home applicants with eligible qualifications who self-identify as being a member of a Black, Asian or Minority Ethnic group will be invited to a Panel interview for their chosen project(s). When the department acknowledges your application, you will have an opportunity to declare this information if you wish. More information about the YCEDE project can be provided by Professor Avtar Matharu avtar.matharu@yorkac.uk .
约克大学 PhD position in Polymerases for the synthesis of functionalised oligonucleotides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 will come from the Department of Chemistry or the Chemistry Wild Fund.
Studentships include i) tuition fees, ii) tax-free stipend at the UKRI rate (£19,237 for 2024/25) iii) funding for consumables/training.
Funding duration is 3yrs
Home rate fee payers are eligible for Department of Chemistry funding.
International rate fee payers are eligible for Chemistry Wild Fund.
Offers will state funding source and duration. Not all projects will be funded.
Fee status information: View Website( https://www.york.ac.uk/study/postgraduate-research/fees/status/ )
Please note funding does not include visa costs or NHS surcharge for visa holders.
约克大学Phd申请条件和要求都有哪些？PhD position in Polymerases for the synthesis of functionalised oligonucleotides项目是不是全奖？有没有奖学金？下面我们一起看一下约克大学申请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
You should hold or expect to achieve the equivalent of at least a UK upper second class degree in Chemistry or a relevant related subject. Check the entry requirements for your country( https://www.york.ac.uk/study/international/your-country/ ).
English language requirements.( https://www.york.ac.uk/study/postgraduate-research/apply/international/english/ )
Candidate selection process:
You should hold or expect to receive at least an upper second class degree in chemistry or a relevant related subject
Applicants should submit a PhD application to the University of York by midnight on Sunday 5 January 2025.
Supervisors may contact candidates to arrange further discussion.
Supervisors can nominate up to 2 candidates to be interviewed for the project
The interview panel will shortlist candidates for interview from all those nominated
Shortlisted candidates will be invited to a panel interview between 10-12 February 2025.
The awarding committee will allocate studentships following the panel interviews
Candidates will be notified of the outcome of the panel’s decision by email, including the funding source and duration.
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