23 February 2017
New Group Leader: Jakub Sedzinski
Jakub Sedzinski joins as a new Group Leader to DanStem. Jakub's Research focuses on determining the reciprocal interactions between mechanical forces and genetics during development, homeostasis and regeneration of tissues
Meet the Scientist, a short interview with Jakub Sedzinski:
With Jakub Sedzinski's recruitment, DanStem will comprise of 11 group leaders, all address basic questions in stem cell and developmental biology. The overall aim is developing of new therapies for cancer and chronic diseases, such as diabetes, Parkinson’s disease and liver failure.
What are the scientific questions you wish to answer?
My primary interest lies in determining the reciprocal interactions between mechanical forces and genetics during development, homeostasis and regeneration of tissues. It is well known that development and maintenance of epithelial sheets depends upon the regular addition of new cells and removal of old cells. However, while the last decade has seen an explosion of interest in the mechanisms governing the homeostatic extrusion or delamination of cells from epithelia, far less is known of the converse process of epithelial cell renewal. This gap in our knowledge is significant because homeostasis of many epithelial tissues involves the addition of new cells from basally-located progenitors. Indeed, such basal stem cells have been described in the airway, olfactory epithelium, cornea, and prostate, among others. In such multilayered tissues, nascent cells must move apically and insert individually and seamlessly into the epithelial sheet, a process that must be exquisitely coordinated in order to maintain epithelial function. In each case, a nascent cell must not only define an apical domain, but must also build a new apical surface of sufficient size to accommodate its function. One major unresolved question concerns force generation during epithelial cell renewal. What are the mechanisms that expand the growing apical surface of individual cells? Moreover, how do new cells generate force to displace the neighboring cells that abut them? These questions about addition of new cells to epithelial are important because the answers will provide an essential complement to the burst of recent studies elucidating mechanisms of force generation during extrusion of old cells from epithelia and most importantly will provide key insights into mechanisms of epithelial homeostasis.
Tell us about your scientific activities in the past years.
Over the past six years I have worked as a postdoc at the University of Texas at Austin, USA. Here, I have begun to unravel both genetics and cell biological mechanisms underlying a fundamental problem of how progenitor cells are added to the existing epithelium. Through the combination of experimental and theoretical work, I have demonstrated that assembly of an apical cell surface is an essential prerequisite for new epithelial cells to assume their specialized function. We coined a term “apical emergence” to describe a broad spectrum of cellular processes by which a single cell’s apical surface emerges, displacing neighbors, and joining an existing epithelium. In addition to describing this novel cell behavior that informs our understanding of epithelial homeostasis and epithelial morphogenesis, my work also describes a new molecular mechanism driving epithelial cell shape change. By combining in vivo imaging, advance image processing, molecular manipulations, laser microdissections, and theoretical modelling, I demonstrated that apical emergence relies on a formin and actin-based pushing force. Such pushing by actin polymerization has been the subject of much theory, and has been examined in mesenchymal cell crawling, but has not ben implicated in epithelial cell shape change, especially in vivo. Overall, my work sheds new light on how multilayered epithelia renew themselves, emphasizing the importance of the molecular and the mechanical regulation of actin network assembly, a driving force of an important cell behavior, apical emergence.
Why did you choose to join DanStem?
I was looking for an interactive environment, with state-of-the-art equipment, and the possibility to work with developmental biologists, system biologists and physicists to further understand mechanisms of epithelial cell renewal. DanStem has all that! The collaborative efforts of the researchers at DanStem also allow me to broaden my scientific vision and encourage trying new directions, which is particularly important for a new group leader.
What are the most important factors for you at a work place?
I strongly believe in a collaborative work. The interdisciplinary nature of the science nowadays requires the intersection of various areas of expertise. Thus, I think it is important to interact with specialists of multiple disciplines to learn how to “speak their language”.
Could you tell us something interesting/ surprising about yourself?
Back in Austin I joined the triathlon team. Despite the fact that I am still a really bad swimmer, I do like this sport; I look forward to triathlon events in Denmark!