My ultimate scientific aim is to contribute to the understanding of diseases, and I believe that in order to achieve this goal we need to understand fundamental cell biophysical mechanisms underpinning health. My lab applies a biophysical approach to studying how cytoskeletons (actin, microtubules and spectrin) collaborate in the establishment of cell polarity and tissue architecture at the mesoscale level. We use Drosophila as a model system to study the role that cytoskeletal forces, and their functional crosstalk, play in the development of the female germline, although we are also exploring the impact of our findings in other tissues (e.g., neurons) and organisms (e.g., mouse oocytes), in a collaborative manner.
Research in cell biology has become increasingly quantitative, and some areas, such as studying the highly dynamic cytoskeletons at the tissue level, require interdisciplinary collaborations. We are successfully collaborating with experimental and theoretical physicists, which allowed us to tackle the role of cytoskeleton dynamics on cellular self-organisation and tissue morphogenesis from a multidisciplinary point of view.
More specifically, there are two available PhD projects. The first one aims to understand the biophysical properties of the interplay between actin and microtubules in cells that are immobile and not dividing. We are studying the biophysical features of this interplay in the Drosophila oocyte, where the crosstalk between the two cytoskeletons impacts on the mechanical properties and self-organization of the female germline, and ultimately on its polarization and function. To further understand the coupling between motor-induced forces, fluid dynamics and cytoskeletal organisation, we are also extending our analysis to super-resolution microscopy and advanced motion and image analysis, as well as to the mouse oocyte. This interdisciplinary approach will allow the student to cover various aspects of quantitative biology, physical modelling and experimental design required to study the relation between the fluid mechanical properties of the cytoplasm and oocyte polarity.
The second project focuses on studying the role of the Spectrin cytoskeleton in epithelium architecture. The spectrin membrane skeleton is a mechanically deformable network, that crosslinks actin to the membrane, and although it has been greatly studied in erythrocytes, little is known about the function of this cytoskeleton in epithelia. We are studying the role of the spectrin cytoskeleton during epithelia morphogenesis using the Drosophila follicular epithelium as a model system. This germline-surrounding epithelium, which is essential for oocyte polarity, has emerged as a powerful model to study epithelial morphogenesis. Spectrins are conserved in all eukaryotes, with a greater conservation between Drosophila and mammalian non-erythroid spectrins than between erythroid and non-erythroid forms. We identified a primary role for the spectrin skeleton in controlling cell shape, specifically cell elongation. Furthermore, the spectrin cytoskeleton is key to maintaining a mono-layered epithelium, as spectrin mutant cells form a “tumour-like” multi-layered mass. We have found that increasing and reducing the activity of the actomyosin cytoskeleton enhances and decreases spectrin multi-layering phenotypes, respectively. Our hypothesis suggests that the spectrin cytoskeleton is essential to balance adequate forces, probably by modulating the actomyosin cytoskeleton, in order to maintain cell shape and epithelium architecture. We are currently studying the distribution of forces in the follicular epithelium, and how this distribution is related to the function of spectrins in regulating the actomyosin cytoskeleton.