Supervisor name: Dr. Fengzhu Xiong
Project 1: Tissue mechanics in body axis symmetry
Xiong Lab is interested in the role and regulation of tissue mechanics in morphogenesis (shape change) during development. We integrate a variety of tools from imaging to soft matter physics with the long-term goal of quantitatively predicting morphogenesis. Early vertebrate embryos increase the length of the body significantly in a relatively short amount of time during somitogenesis while maintaining straightness. This straightness is fundamental to the correct shapes of body axis tissues such as the neural tube, and is also important for a balanced body movement and may underlie certain developmental defects (e.g., idiopathic scoliosis). Different tissues including neural and mesodermal contribute mechanical forces to the axis elongation. However, the cell dynamics and tissue forces in these tissues that prevent axis curvature remain unknown. This PhD project will employ an interdisciplinary approach aiming at exposing the student to modern methods in developmental biology including live imaging, mechanics and modeling. The approaches include but are not limited to: observing and analyzing the dynamics and variability of tissue symmetry and cell behaviours in avian embryos; performing microsurgeries and quantitative tissue force measurements to understand the mechanical constraints on the body axis; developing computational models linking signalling, cell dynamics to tissue mechanics to assess robustness of symmetry.
Project 2: Genetic regulation of tissue mechanics
Xiong Lab is interested in the role and regulation of tissue mechanics in morphogenesis (shape change) during development. We ask what are the ranges of stresses developing tissues produce / can sustain? What signaling pathways regulate tissue mechanical properties? How do certain hallmark development processes respond to changing forces? What are the genetic and biochemical changes underlying those responses? Answering these questions is key to derive the principles of tissue shape control that underlie tissue/organ engineering and regenerative medicine. We will use soft gels, magnetic droplets and cantilevers to detect and impose forces in the soft tissues of the early avian embryos, whose large size and accessibility provide a suitable model for these applications. Additional possibilities include engineered extracellular matrix and micro-robots (with collaborations and training opportunities internationally), or novel ideas conceived by the student. Following mechanical perturbations, we will analyze the cell responses by immunohistochemistry, molecular sensors, QPCR or sequencing. These approaches will lead to novel findings that link both novel and classic developmental pathways to tissue mechanics, which directly control morphogenesis. This PhD project will focus on testing a specific hypothesis of mechanical regulation from identified genetic players. We anticipate to reveal non-intuitive feedbacks across scales that control robust morphogenesis on the complex systems level.
Relevant references:
1. Xiong, Fengzhu, et al. "Mechanical Coupling Coordinates the Co-elongation of Axial and Paraxial Tissues in Avian Embryos." bioRxiv (2018): 412866.
2. Mongera, Alessandro, et al. "Mechanics of Anteroposterior Axis Formation in Vertebrates." Annual review of cell and developmental biology 35 (2019): 259-283.
3. Xiong, Fengzhu, et al. "Interplay of cell shape and division orientation promotes robust morphogenesis of developing epithelia." Cell 159.2 (2014): 415-427.