Elucidating the Molecular Mechanisms of Mechanical Memory at Queen Mary University of London on FindAPhD.com

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Dr Isabel Palacios, Dr J Gautrot No more applications being accepted Awaiting Funding Decision/Possible External Funding

London United Kingdom Biochemistry Biophysics Cell Biology Molecular Biology

About the Project

Research environment

The School of Biological and Behavioural Sciences at Queen Mary is one of the UK’s elite research centres, according to the 2014 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.

The Gautrot lab is an expert on the design of novel biomaterial to be used for the reconstruction of artificial micro-environment for tissue engineering and regenerative medicine, while the Palacios lab is an expert on studying the organisation of cells and tissues in vivo. Together they have more than 100 research articles, in journals such as Nature, Nat Comm., Chem Rev, Nat Mater, and Nat Cell Biol. Particularly relevant achievements from these labs include work on implementing novel physical approaches to quantitative analysis of cytoskeletal dynamics, and understanding the impact of physical properties of the cell microenvironment (mechanics, topography, geometry) on cell adhesion and phenotype. Both labs have had many Masters and PhD students, as well as Postdoctoral researchers.

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.

The student will become an expert on cell and tissue visualisation approaches, quantitative cellular and physical perturbations, and theoretical concepts to study the biophysics of migrating cells.

Project description

This project builds on a recently established interdisciplinary collaboration between Isabel M Palacios (IP, School of Biological & Behavioural Sciences, SBBS) and Julien Gautrot (JG, School of Engineering & Materials Science, SEMS) at QMUL. Cells can sense the mechanical properties of their microenvironment. Such sensing has a profound impact on cell phenotype during development, tissue homeostasis and in pathological scenarios. In addition, recent data showed that cells can retain mechanical information for prolonged periods of time: mechanical memory is emerging as a process via which mechanical (potentially physical) information from the cell microenvironment remains stored for prolonged periods of time in the form of a biochemical information.

We propose that spatially and temporally coordinated mechanical memory plays a broader role in defining cellular phenotypes in development. However, the molecular mechanisms underlying mechanical memory remain poorly understood and mostly unexplored. This project will identify how mechanical memory of migrating macrophages during embryogenesis impacts on their final differentiation and function.

To study the molecular mechanisms of mechanical memory, we propose to combine in vivo and in vitro engineered 3D microenvironments. We will: (i) Identify molecular mechanisms underpinning the retention of mechanical memory. (ii) Decipher the impact of mechanical memory on migratory phenotypes during development. We will study the impact of the mechanical landscape along the migratory pathway of macrophages on mechanical memory, and on the final adult phenotype of those macrophages.

Eligibility and applying

Applicants must:

Be Chinese students with a strong academic background.
Students must hold a PR Chinese passport.
Applicants can either be resident in China at the time of application or studying overseas.
Students with prior experience of studying overseas (including in the UK) are eligible to apply. Chinese QMUL graduates/Masters’ students are therefore eligible for the scheme.

Please refer to the CSC website for full details on eligibility and conditions on the scholarship.

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. Applicants need to have a passionate interest in studying cell behaviour in healthy and pathological scenarios, as well as wanting to explore the biophysical properties of cells and tissues as a mean to ultimately understand diseases.

Applicants are required to provide evidence of their English language ability. Please see our English language requirements page for details.

The deadline for applications to Queen Mary is 30th January 2022. Applicants will need to complete an online application form by this date to be considered, including a CV, personal statement and qualifications. Shortlisted applicants will be invited for a formal interview by the project supervisor. Those who are successful in their application for our PhD programme will be issued with an offer letter which is conditional on securing a CSC scholarship (as well as any academic conditions still required to meet our entry requirements).

Once applicants have obtained their offer letter from Queen Mary they should then apply to CSC for the scholarship by the advertised deadline with the support of the project supervisor. For September 2022 entry, applicants must complete the CSC application on the CSC website between 10th March - 31st March 2022.

Only applicants who are successful in their application to CSC can be issued an unconditional offer and enrol on our PhD programme.

Apply Online

Funding Notes

This studentship is open to students applying for China Scholarship Council funding. Queen Mary University of London has partnered with the China Scholarship Council (CSC) to offer a joint scholarship programme to enable Chinese students to study for a PhD programme at Queen Mary. Under the scheme, Queen Mary will provide scholarships to cover all tuition fees, whilst the CSC will provide living expenses for 4 years and one return flight ticket to successful applicants.

References

1. You, Y.; Kobayashi, K.; Colak, B.; Luo, P.; Cozens, E.; Fields, L.; Suzuki, K. and Gautrot, J.E. “Engineered Cell-Degradable Poly(2-alkyl-2-oxazoline) Hydrogel for Epicardial Placement of Mesenchymal Stem Cells for Myocardial Repair” Biomaterials 2021, 269, 120356.
2. Wu, L.; Di Cio, S.; Azevedo, H. and Gautrot, J.E. "Photo-Configurable, Cell-Remodelable Disulfide Crosslinked Hyaluronic Acid Hydrogels" Biomacromolecules 2020, 21, 4663.
3. Ng BF, Selvaraj GK, Santa-Cruz Mateos C, Grosheva I, Alvarez-Garcia I, Martín-Bermudo MD and Palacios IM (2016). Alpha-Spectrin and Integrins act together to regulate actomyosin and columnarization, and to maintain a mono-layered follicular epithelium. Development. Apr 15;143(8):1388.
4. Drechsler M, Giavazzi F, Cerbino R and Palacios IM. Active diffusion and advection in the Drosophila ooplasm are due to the interplay of the microtubule and actin cytoskeletons. Nature Communications 2017, Nov 15;8(1):1520.
5. Francis D, Chanana B, Fernandez B, Gordon B, Mak T, and Palacios IM. YAP/Yorkie in the germline modulates the age-related decline of germline stem cells and niche cells. PLoS One 2019. Apr 3;14(4).
6. Santa-Cruz Mateos C, Valencia-Expósito A, Palacios IM, and Martín-Bermudo MD. Integrins regulate epithelial cell shape by controlling the architecture and mechanical properties of basal actomyosin networks. PLoS Genet 2020. Jun 1;16(6):e1008717.
7. Drechsler M, Lang LF, Al-Khatib L, Dirks H, Burger M, Schönlieb CB, Palacios IM. Optical flow analysis reveals that Kinesin-mediated advection impacts on the orientation of microtubules. Mol Biol Cell 2020 Jun 1;31(12):1246.