Group: Pluripotency for organ regeneration and Integrative cell and tissue dynamics
Group leader: Núria Montserrat (firstname.lastname@example.org) and Xavier Trepat (email@example.com)
The proposed project will encompass a new collaboration between the Integrative Cell and Tissue Dynamics Group directed by Prof. Xavier Trepat and the Pluripotency for Organ Regeneration Group led by Dr. Nuria Montserrat, both at IBEC.
We propose the use of human pluripotent stem cells (hPSC)-derived kidney organoids as an unprecedented human in vitro model to provide a mechanistic understanding of early steps of nephron formation (namely, patterning and segmentation). Recent work from our laboratories has shown that tightly controlling the mechanochemistry of cell-cell and cell-extracellular matrix interactions results in the generation of higher-grade hPSC-derived kidney organoids (1). Based on these findings we hypothesize that renal cell fate specification and nephron patterning may arise from a combination of force generation and transduction through biochemical and biophysical signaling. Since the interplay between these fundamental cues remains to be explored in multicellular systems (as hPSCs-derived kidney organoids) this project will allow us to combine quantitative, real time imaging (through the development of reporter cell lines using CRISPR/Cas9 technologies) and force mapping to spatiotemporally analyze the dynamics of multicellular interactions during self-driven nephron formation in developing hPSC-derived kidney organoids. Furthermore, we aim to use computational modelling for deconstructing crucial state transitions observed experimentally during nephron formation in hPSCs-derived kidney organoids (differentiation of renal vesicle to “comma” shape body, or s-shape bodies to nephron-like state).
Overall, our aim is to predict emergent multicellular behaviors when perturbing the experimental system with external inputs (i.e. forcing/limiting boundary conditions, providing different substrate stiffness mimicking embryonic and disease-like contexts, biochemical signaling, among others).
(1) Nat. Mater. 2019, 18, 397–405.
We are looking for highly motivated PhD students to work on the fundamental understanding of the biophysical and biochemical mechanisms leading to kidney development and dysfunction.
It is expected that the student will contribute to common lab supporting tasks, research collaborations, recording and reporting processes, as well as publications and other scientific communications derived from this work (outreach activities, among others).
The student will use a wide range of concepts and methods encompassing the fields of stem cell biology, cell mechanics, biochemistry, molecular and cellular biology, and molecular biology techniques, analytical tools and drug targeting, etc.
Applicants should possess a strong background in molecular and cell biology or physics, or associated disciplines. Specific experience in the fields of stem cells development/biology and/or physics will be an advantage.