Meet the new researchers joining LSI

Already during his PhD studies with Markus Affolter at the Biozentrum (Basel, Switzerland) Stefan developed an interest in how biological size is controlled during animal growth, studying how molecular gradients control the growth of fruit flies wing. During his postdoctoral work in the group of Thomas Lecuit at the IBDM in Marseille (France) he subsequently focused on the emergence of biological shape. Within the interdisciplinary context of the Turing Center for Living Systems (Centuri) Stefan demonstrated the importance of the extracellular matrix (ECM), an intricate network of extracellular macromolecules, for fruit fly wing development. In particular, his work uncovered that the dynamic growth properties of the ECM, a previously neglected aspect, is instructive for guiding functional tissue shape.

For his future research at LSI, Stefan aims to combine his background in growth and shape control to uncover the biophysical basis of biological shape generation during organ growth. His work will focus on the mechanical interaction between growing tissues and their ECMs, essential in determining the mechanical properties of growing tissues. Using an interdisciplinary approach, combining classical fruit fly genetics with state-of-the-art high-resolution microscopy and biophysical methods, Stefan’s group aims to uncover how the material properties of the extracellular matrix mechanically guide the morphology of developing epithelial tissues. 

Stefan is convinced that the LSI provides a unique environment, facilitating cross-discipline interactions, that will be instruments for putting his scientific vision into reality. In particular, Stefan is excited to push work at the interface of developmental biology, biophysics and engineering, establishing collaborations within LSI and with teams in the neighbouring physics and engineering department. With his interdisciplinary approach to ECM-guided shape generation Stefan aims to uncover the basic mechanical principles of morphogenesis that will not only push our understanding of biological shape generation but also holds potential for future applications in tissue engineering and regenerative medicine.

I'm a developmental biologist and geneticist by training, but I have later used omics methods with a systems biology approach. I got my PhD in the department of genetics of the university of Barcelona (genetics/developmental biology), which happens to be a hotspot for planarian research. Then I was postdoc for 2 years in the university of Nottingham (UK) and then 6 years in the Berlin Institute for Medical Systems Biology (BIMSB, part of MDC Berlin, Germany) where I got in touch with the omics and systems biology approaches. Then, I started my independent research group at Oxford Brookes university.

I'm interested in stem cells and how these work in the process of animal regeneration. Unlike humans, many invertebrates are able to regenerate lost or injured body parts. Some regenerative animals are unable to regenerate all body parts. For instance, salamanders can regenerate limbs and tails, but cannot regenerate heads or trunks. However, (and very interestingly for me) some others can regenerate just any body part. This is the case of the planarian Schmidtea mediterranea, the main model system of the lab, but also other animal models that my research group is using, pioneering or establishing. This is the case of the annelid Pristina leidyi, the cnidarian Hydractinia symbiolongicarpus and the ascidian Botryllus schlosseri, all of which we will use at the LSI. 

The reason why these animals can regenerate and we cannot is most likely the presence of pluripotent stem cells in their adults. These are cells that can give rise to all other adult cell types. Us, humans, and mammals in general have pluripotent stem cells only in our very early stages of developing (essentially in the first week of pregnancy) and then they're gone forever. Several groups at LSI are experts in human and mammalian pluripotent stem cells (Austin Smith, Ge Guo, Akshay Bhinge). But planarians (and likely annelids, cnidarians and ascidians among others, but this is not yet well understood) have pluripotent cells throughout their adult life and use them to regenerate.

The problem is : we have historically lacked methods to study stem cell pluripotency in animals that are not well established model organisms. Recently novel techniques of single cell sequencing have emerged and allow identifying animal stem cells and elucidating how many cell types they can differentiate into. I participated in the team that characterised the cell type atlas of S. mediterranea for the first time, one of the first cell type atlases by single cell sequencing. As an independent group leader we have optimised new, better methods of single cell sequencing. Now, at LSI, we aim at using these methods to study pluripotent stem cells in a variety of regenerative model organisms and understand how they orchestrate animal regeneration. 

My group uses systems biology, single cell approaches. These are emerging now and soon will necessitate more complex mathematical treatment and be used for biological modelling. The LSI is very rich in those sorts of approaches, and I'm excited about interacting with these groups in the next few years, as they can get single cell analysis to a whole new level. Furthermore, the LSI has outstanding facilities including cytomics (key for our single cell work), imaging (key for putting back our computational findings into the spatial organisation of the animals), sequencing (key for our omics, sequencing approach) and aquatic culture (key to upscale the number of species we can study). Finally, as stated above, several LSI groups are leaders in pluripotent stem cell research. Interactions with these groups can advance our knowledge on the most fundamental questions: are pluripotent stem cells of humans similar to those of regenerative animals like planarians? And why then can they regenerate while we can't? Ultimately, can we leverage this knowledge to improve human injury and advance regenerative medicine?

Nikolas is a neurobiologist with a strong background in developmental biology, neuroanatomy and molecular genetics. As a PhD student at the MRC National Institute for Medical Research he investigated cell signalling mechanisms regulating the balance between neural progenitor maintenance and differentiation in the developing nervous system. Nikolas did his postdoctoral research at the Centre for Developmental Neurobiology (King’s College London) investigating molecular and cellular mechanisms regulating neuronal wiring in the larval zebrafish brain. Nikolas stared his independent research group at the University of Bath before moving to Exeter.

Nikolas aims to combine his background in developmental neurobiology and zebrafish as a genetic model organism to uncover novel processes that influence the development and function of the nervous system. His work will focus on the role of RNA regulators in extra-nuclear neuronal compartments and how their activity controls aspects of local RNA processing. Using an interdisciplinary approach, combining zebrafish genetics with state-of-the-art structural and functional imaging techniques, biophysical methods and mathematical modelling, Nikolas’s group aims to elucidate mechanisms essential for brain connectivity and how these are affected in neurological disease conditions. 

Nikolas chose LSI for its interdisciplinary environment. His group uses molecular cell biology, genetic and imaging approaches to investigate the molecular, cellular, and structural basis of brain development and nervous system activity. However, obtaining a comprehensive understanding of how the nervous system works requires insights from multiple scientific disciplines. Therefore, interdisciplinary research is essential in Nikolas’s research. In particular, Nikolas is excited to work at the interface between developmental neurobiology, biophysics, and mathematical modelling, establishing collaborations with other LSI researchers. Through these collaborations, Nikolas aims to advance the knowledge on the most fundamental questions in neuroscience: how do neurons grow and establish connections with their correct targets during development? What intrinsic and extrinsic molecular signals guide axons and dendrites to form synapses? How dysfunctions in such processes lead to neurological disease conditions? Ultimately, can we utilise knowledge gained to reverse such conditions in the brain?