Chemical biology approaches to study and modulate protein phosphatases
- Supervisors: Dr Elena De Vita and Prof. Viji Draviam
- Funding: SBBS Start-up Studentship
- Deadline: 31st July 2023
The following fully-funded PhD studentship is available in the School of Biological and Behavioural Sciences with an expected start date of Jan 2024
Research environment
The School of Biological and Behavioural Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2021 Research Excellence Framework (REF). We offer a multi-disciplinary research environment and have approximately 150 PhD students working on projects in the biological and psychological sciences. Our students have access to a variety of research facilities supported by experienced staff, as well as a range of student support services.
Dr Elena De Vita is a medicinal chemist and chemical biologist, with a track record in developing covalent chemical probes to study emerging drug targets.
The new Chemical Biology group at the SBBS will focus on developing approaches to characterise protein phosphatases activity in cancer models with the aim of developing novel chemical probes to modulate protein phosphatase activity in physiology and disease.
Training and development
Our PhD students become part of Queen Mary’s Doctoral College which provides training and development opportunities, advice on funding, and financial support for research. Our students also have access to a Researcher Development Programme designed to help recognise and develop key skills and attributes needed to effectively manage research, and to prepare and plan for the next stages of their career.
You will be joining a highly interdisciplinary research group with the opportunity to develop skills at the interface of chemistry and biology. Specifically, you will be trained in organic synthesis and molecular and cell biology techniques, gaining an understanding of the chemical probe development process from model system identification to design and optimisation.
Furthermore there is an opportunity to aquire microscopy-related training thanks to the co-supervision of Prof Viji Draviam, who is an established leader in the field.
Project description
Protein phosphorylation is a post-translational modification that controls protein function by altering protein charge state, which regulates structural conformation and/or interacting partners. Protein kinases (PKs) catalyse phosphorylation and phosphatases (PPs) catalyse dephosphorylation, thereby regulating phosphosignalling cascades. Compared to the advancement of the PK field, characterising and modulating PP function remains elusive.
Our research will focus on the development of specific chemical probes to study and control cellular dephosphorylation. Being able to modulate the protein phosphorylation state by hijacking protein phosphatase function will provide new avenues for drug discovery approaches in diseases characterised by hyperphosphorylation, such as cancer and neurodegenration.
Initially, the student will develop and synthesise targeted covalent probes to study an ubiquitously expressed PP that has been shown to be amenable to targeted protein dephosphorylation (Yamazoe et al. 2020). These probes will be used to characterise PP function and localisation in cell, using chemical proteomics and phosphoproteomics as well as fluorescence microscopy in collaboration with Prof Draviam.
In a second stage of the project, the developed probes will be further used in the design of heterobifunctional molecules that are able to direct a specific protein for targeted dephosphorylation. These compounds will be used to characterise this novel proximity-based modality and will be applied to tackle challenging targets in cancer drug discovery.
Funding
The studentship is funded by Queen Mary and will cover home tuition fees, and provide an annual tax-free maintenance allowance for 3 years at the UKRI rate (£20,622 in 2023/24).
For international students interested in applying, please note that this studentship only covers home tuition fees and students will need to cover the difference in fees between the home and overseas basic rate. Further details can be found here: https://www.qmul.ac.uk/postgraduate/research/funding_phd/tuition-fees/
Eligibility and applying
Applications are invited from outstanding candidates with or expecting to receive a first or upper-second class honours degree in an area relevant to the project. A masters degree is desirable, but not essential.
The successful candidate is expected to have a background in chemistry or chemical biology, experience with organic synthesis and biochemical assays and at least a general understanding of biological sciences concepts. Good organisatorial and problem-solving skills and the capability to work independently under supervision are essential.
Previous experience in tissue culture and molecular biology is desirable but not required. Highly driven candidates with a passion for solving scientific questions of any background are strongly encouraged to apply.
Applicants from outside of the UK are required to provide evidence of their English language ability. Please see our English language requirements page for details: https://www.qmul.ac.uk/international-students/englishlanguagerequirements/postgraduateresearch/
Informal enquiries about the project can be sent to Dr Elena De Vita - e.devita@qmul.ac.uk Formal applications must be submitted through our online form by 31st July 2023
The School of Biological and Behavioural Sciences is committed to promoting diversity in science; we have been awarded an Athena Swan Silver Award. We positively welcome applications from underrepresented groups.
http://hr.qmul.ac.uk/equality/
https://www.qmul.ac.uk/sbcs/about-us/athenaswan/
References
- Fahs S, Lujan P, Köhn M. Approaches to study phosphatases. ACS Chem Biol. 2016;11(11):2944-2961;
- Chatterjee J, Beullens M, Sukackaite R, et al. Development of a peptide that selectively activates protein phosphatase-1 in living cells. Angew Chemie - Int Ed. 2012;51(40):10054-10059;
- Fontanillo M, Trebacz M, Reinkemeier CD, et al. Short peptide pharmacophores developed from protein phosphatase-1 disrupting peptides (PDPs). Bioorg Med Chem. 2022;65:116785;
- Yamazoe S, Tom J, Fu Y, et al. Heterobifunctional Molecules Induce Dephosphorylation of Kinases-A Proof of Concept Study. J Med Chem. 2020;63(6):2807-2813;
- Conti, D, Gul, P, Islam, A, et al. Kinetochores attached to microtubule-ends are stabilised by Astrin bound PP1 to ensure proper chromosome segregation. eLife 2019, 8:e49325.