Harmansa Group We are recruiting! Two open PhD projects supported by the LSI PhD program (details below). Applications open on the 9th of April! Morphomechanics – Shaping Growing Tissues Morphogenesis delineates the complex process of shape generation during embryonic development. Morphogenesis is an intrinsically mechanical process where cellular activities, like contractility or growth, lead to stresses that mechanically mould tissues into their complex 3D shapes. Proper morphology is essential for organ functionality and defects in morphogenesis are linked to developmental disorders and disease. We are particularly interested in the interplay between growing epithelial tissues and their basement membranes (BMs), specialised sheet-like extracellular matrices. Like the foundation of a building, BMs acts as base for epithelial cells and their mechanical properties (such as stiffness) as well as their growth properties directly influence cell and tissue morphology. We recently demonstrated that differential growth between a tissue and its BM leads to the accumulation of growth-induced mechanical stresses that guide tissue morphology (Harmansa et.al. 2023). Using a combination of Drosophila genetics, advanced imaging techniques, quantitative biophysical tools and data-informed modelling we aim to uncover how such stresses arise during tissue growth and how they guide the mechanics of morphogenesis. We are a newly established group that officially joined LSI in February 2024 and we will be supported by a Wellcome Career Development Award given to Stefan Harmansa. For more details on our current research, news and open positions please visit our group’s webpage. Our new preprint is online – ‘Mechanical regulation of cuboidal-to-squamous epithelial transition in the Drosophila developing wing’ We are looking for PhD students to join our growing research team. The two studentships are supported by the LSI PhD program and applications will open on the 9th of April. PhD Project 1 – ‘How to make an eye – mechanics of optic cup formation’ Co-supervised by Prof. Steffen Scholpp and Dr. David Richards Project summary – Morphogenesis is driven by mechanical forces, with the basement membrane (BM) playing a key role in epithelial tissue stability and shape. Collagen IV, the BM’s main structural component, is essential for stress generation during optic cup formation, but its biomechanical contributions remain unclear. This PhD project will investigate how BM structure and Collagen IV dynamics drive early vertebrate eye development using zebrafish. Combining live imaging, genetic manipulations (CRISPR), biophysical techniques (AFM, laser ablation), and computational modelling, this interdisciplinary project offers training at the interface of biology, physics, and mechanics, with implications for collagen-related diseases and tissue engineering. Lay summary – Our eyes begin as simple cell sheet that must bend and fold forming the complex structures needed for vision. A key player in this process is the basement membrane (BM), a thin but sturdy layer that provides crucial support to developing tissues. Mutations affecting Collagen IV, a major BM component, weaken this structure and lead to eye defects, kidney disease, and vascular disorders. Using zebrafish, whose transparent embryos allow real-time imaging, this project will reveal how BM mechanics shape organ formation. These insights could advance our understanding of birth defects and inspire new strategies for regenerative medicine and disease treatment. Get in touch with Stefan for more details or to informally discuss the project (s.harmansa@ exeter.ac.uk). PhD Project 2 – ‘Growing to size – Mechanical feedback in organ growth control’ Co-supervised by Prof. James Wakefield and Dr. David Richards Project summary – This PhD project will investigate how organ growth arrest is regulated during development, a key process that, when disrupted, contributes to diseases such as cancer. While growth factors and morphogens are known regulators, emerging evidence suggests that mechanical feedback contributes to growth control. Using the Drosophila wing disc, you will explore whether basement membrane (BM)-generated mechanical stress contributes to growth arrest. You will employ Drosophila genetics, advanced microscopy, biophysical assays and mathematical modelling to relate BM and tissue mechanics to growth. This interdisciplinary project integrates developmental biology, biophysics and modelling, providing training across multiple techniques addressing a fundamental biological question. Lay summary – How do organs grow to the correct size, and why does this control fail in diseases like cancer? While chemical signals help regulate organ growth, emerging evidence highlights the impact of physical forces within tissues for growth control. This project will investigate how mechanical stress originating from the extracellular matrix influences growth dynamics and final arrest. By combining fly genetics, biophysics and computational modelling, we aim to uncover universal principles of growth control. Understanding these fundamental mechanisms could provide new insights into developmental disorders, inspire cancer treatments and inform strategies for engineering tissues. Get in touch with Stefan for more details or to informally discuss the project (s.harmansa@ exeter.ac.uk). Want to join us? Are you excited by the huge diversity of shapes observed in biological systems and how they are generated? Would you like to work in an interdisciplinary environment and bridge between biology, physics and scientific computing? Then come and join our young and dynamic team in beautiful Exeter.We are always looking for innovative, passionate and motivated undergraduate students, graduate students and postdocs with a strong interested in the biophysical aspects of shape generation during animal development. In addition to the official openings, we always welcome spontaneous candidatures for internship, master, Ph.D. and postdoc positions. Please get in touch with Stefan if you you would like us to host your own PhD project (e.g. LSI PhD Programme) or postdoctoral fellowship (e.g. Wellcome Early Career Award or HFSP Cross Disciplinary Fellowships). In general, you can always contact Stefan (s.harmansa@exeter.ac.uk) to inquire about general information and future openings. Alumni Jessica Jarvis (internship summer 2024) Theodore Natusch (internship summer 2024)