29 June 2018
Department of Immunology, Genetics and Pathology
Uppsala University, Sweden
How long does it take cells to collectively make a decision? And how do local tissue conditions impact the speed of collective deliberations, and the subsequent morphogenesis they control? These are the questions I will focus on, considering specifically how endothelial cells decide when and where to extend new blood vessel branches during angiogenesis in a variety of normal and pathological conditions.
The process of new blood vessel growth (angiogenesis) is highly dynamic, involving complex coordination of multiple cell types. Though the process must carefully unfold over time to generate functional, well-adapted branching networks, we seldom hear about the time-based properties of angiogenesis, despite timing being central to other areas of biology. Here, we show using predictive agent based modeling integrated with in vitro and in vivo experiments that tissue conditions can locally adapt the timing of collective cell behaviours/decisions to grow different vascular network architectures. A growing array of seemingly unrelated 'temporal regulators' are predicted by our model and have subsequently been validated in vivo, including tissue derived factors (e.g. semaphorins or the high levels of VEGF found in cancer) and cellular processes (e.g. asymmetric cell division or filopodia extension) that act to alter the speed of cellular Notch regulated decisions to migrate. I will discuss how 'temporal adaptation' provides a novel account of organ/disease-specific vascular morphology and reveals 'timing' as a potential new target for therapeutics.
current theory lunch schedule