Nano-Enhanced Hydrogels for Probing Cellular Mechanotransduction

The selected candidate will conduct interdisciplinary research under the supervision of Prof. Susana Rocha (KU Leuven, Belgium) and Dr. James Hutchison (Melbourne University, Australia). This role involves joining the Molecular Imaging and Photonics division at the Department of Chemistry (KU Leuven) and the School of Chemistry (University of Melbourne).
Prof. Rocha's group specializes in advanced microscopy and nanoscopy to address biologically relevant challenges. Our research focuses on biomimetic hydrogels that replicate the extracellular matrix (ECM) to study how mechanical signals influence cell behavior. We use (super-resolution) fluorescence imaging to investigate cell-ECM interactions, providing crucial insights into fibrosis and cancer metastasis. Additionally, the group develops nanoparticle-based systems for drug delivery and intracellular tracking, aiming to improve tissue engineering and regenerative medicine applications.

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Project

Cells continuously interact with their microenvironment, sensing and responding to mechanical properties and cues, which in turn regulate cellular behavior. This interaction is a bidirectional process; cells not only perceive mechanical signals but also actively remodel the extracellular matrix (ECM), aligning and densifying its fibers, which alters the ECM’s mechanical properties. This dynamic feedback loop between cells and the ECM is critical in many physiological and pathological processes, particularly in diseases such as lung fibrosis, where aberrant ECM remodeling leads to tissue dysfunction. Despite its recognized importance in tissue engineering, disease modeling, and regenerative medicine, fully deciphering the cell-ECM interplay remains challenging. This is partly due to the lack of precise tools to quantify the dynamic mechanical changes in the ECM at the micron and nanoscale. Our research aims to bridge this gap by employing passive and active microrheology. We plan to leverage the creation of advanced nanoparticles and the application of sophisticated microscopy techniques to investigate this phenomenon. By using synthetic biomimetic materials that mimic various ECM properties and engaging cells in different activation states, such as fibroblasts activated by TGF-β, we intend to observe and quantify cell-induced mechanical changes. It is anticipated that the insights gained from this research will not only elucidate the mechanisms underlying fibrosis but pave the way to understanding cell-ECM interaction in other diseases.

This project is part of a Global PhD partnership between KU Leuven and Melbourne University, where 2 PhD students will be involved. The goal of this joint PhD program proposal is to develop methods to probe and control the mechanical properties of synthetic ECMs at the subcellular scale, opening new research avenues for investigating mechanotransduction pathways in fibrosis. The project will combine advances in: (i) multi-functional, stimuli-responsive nanomaterials, leveraging expertise at the University of Melbourne (UoM); and (ii) biomimetic hydrogels, advanced optical microscopy and lung fibrosis disease models, leveraging expertise at KU Leuven (KUL). The PhD project for which KU Leuven is the home university will focus on the development of microrheology to probe cell-induced changes on the ECM.

Profile

We are seeking highly motivated candidates that hold a master’s degree in (bio)chemistry, (bio)physics or nanotechnology related subjects. Experience with optical microscopes, nanoparticle synthesis, soft matter physics or 3D cell culture is a plus. The candidate should be open to interdisciplinary science and collaborations. KU Leuven offers in this respect an ideal environment with a large number of science groups working on different (applied) subjects. 

Offer

• One fully funded project is available. This Joint PhD project will be primarily based at the KU Leuven with a 18-month stay at the University of Melbourne (anticipated start date: October 2024-March 2025, to be discussed).

• You will be part of an Global Partnership PhD program, joining KU Leuven and the University of Melbourne as a dual PhD student.
• Possibility to work in a multidisciplinary environment in close collaboration with the groups of profs. Rocha, Hofkens, Uji-i and Carlon (KU Leuven). 
• A remuneration package competitive with industry standards in Belgium, a country with a high quality of life and excellent health care system.
• Ample occasions to develop yourself in a scientific and/or an industrial direction. Besides opportunities offered by the research group, further doctoral training for PhD candidates is provided in the framework of the KU Leuven Arenberg Doctoral School (https://set.kuleuven.be/phd).
• A stay in a vibrant environment in the hearth of Europe. The university is one of Europe’s oldest academic institutions and is situated in a medium-sized vibrant student town with a large international community.   

International training groups (KU Leuven - Melbourne)

Interested?

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