School of Biosciences
 

Image of Osvaldo Chara

Osvaldo Chara

Assistant Professor, Faculty of Science

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Biography

My journey to understand how tissues grow and form began during my PhD in Biophysics (University of Buenos Aires, Argentina), where I studied the asymmetric transport of solutes and water in epithelial tissues. Trying to understand my own experiments, I developed mathematical models to test different hypotheses by simulating them. I soon became fascinated by the elegance of modelling the complexity of tissues resulting from the interactions of cellular and molecular collectives. During my postdoctoral and principal investigator positions (University of La Plata, Argentina, and Technische Universität Dresden, Germany), I acquired and refined various mathematical and computational modelling techniques, while fostering an interdisciplinary and integrative approach.

Expertise Summary

Broadly speaking, my expertise lies in the mathematical modelling of complex biological problems. In particular, our lab develops mathematical and computational models of tissues. We are fascinated by how tissues form and grow during development and regeneration.

We use continuous approaches, based on Partial Differential Equations or discrete cell-based multi-scale approaches, such as Interactive Cell Systems, Vertex Models, Cellular Potts Models and other formalisms.

Research Summary

We are fascinated by the challenges posed by the enormous complexity of tissues in terms of their structure, dynamics and functionality in healthy and pathological conditions.

Computational inference of mechanical forces in tissues:

We have recently developed ForSys, a computational tool for dynamic inference of mechanical stresses in tissues (Borges et al., bioRxiv, 2024). A tutorial on how to use ForSys can be found here and here.

How the spinal cord regenerates in the axolotl:

The spinal cord is a remarkable tissue that has fascinated me for many years. In most vertebrates, including humans, severe spinal trauma results in irreversible consequences with loss of function caudal to the site of injury. Remarkably, axolotls can repair spinal cord injuries and even entire tail amputations, achieving complete and faithful regeneration. My research focuses on deriving the governing principles of spinal cord regeneration through formal quantitative analysis and computational/mathematical modelling. Recently, my group has discovered how a reaction-diffusion signal can control spinal cord regeneration in axolotls, and reported for the first time the diffusivity and half-life of the regeneration-inducing signal, in agreement with existing experimental data (Caliaro et al., iScience, 2023). Previously, we developed the first computational model with cell-level spatial resolution of a regenerating and developing spinal cord. This model incorporated the novelty of an internal clock in each cell, representing the position along the cell cycle. To test our model, we designed a transgenic FUCCI axolotl and studied the dynamics of cells along the cell cycle during the regeneration process in collaboration with Leo Otsuki and Elly Tanaka at the IMP in Vienna and Aida Rodrigo Albors in Edinburgh (Cura Costa, Otsuki et al., eLife, 2021). By combining mathematical modelling and image analysis, we were able to determine that axolotl spinal cord regeneration is primarily driven by cell cycle acceleration (Rost, Rodrigo Albors et al., eLife, 2016; Rodrigo Albors et al., eLife, 2015).

Modelling and image analysis in tissues in axolotls and zebrafish:

In several collaborations, the models and image analysis developed in my laboratory have been instrumental in understanding the dynamics of a variety of tissues in axolotl and zebrafish during development and regeneration. A mathematical modelling approach has allowed us to mechanistically explain the process of neuronal cell inversion during division in the zebrafish lateral line, in collaboration with Hernan Lopez-Schier at the Helmholtz Zentrum München (Kozac et al., Development, 2023). In collaboration with Tatiana Sandoval-Guzman at the CRTD/Faculty of Medicine, TUD, we used modelling to address the fundamental question of whether axolotls stop growing during their lifetime and found that they always continue to grow at a decelerated rate (Riquelme-Guzman et al., Developmental Dynamics, 2022). As part of a collaborative study led by Maximina Yun, MPI-CBG and CRTD, my lab developed image analysis software that revealed the spatial distribution of a master regulator that controls the proximal-distal identity of cells in axolotl limbs during regeneration (Oliveira et al., Nature Communications, 2022). Previously, I developed image analysis tools to identify the source of migrating progenitor cells in regenerating axolotl digits and limbs (Currie et al., Developmental Cell, 2016). In a collaborative project with Elly Tanaka, I developed another image analysis algorithm that was used to show that axolotl limb regeneration does not occur by intercalation, but rather gradually (Roensch et al., Science, 2013).

Tissue morphogenesis:

I am particularly interested in the principles governing the control of cell-level mechanisms of proliferation and apoptosis by morphogenetic signals and vice versa. Recently, we discovered that homeostatic tissues, in which proliferation and apoptosis are in equilibrium, represent a critical state that separates the dynamic phases of tissue growth and decay (Lavalle et al., Royal Society Open Science, 2023). Previously, we determined the existence of a critical tissue size that separates two reaction-diffusion regimes of morphogen gradients (Ceccarelli et al., Royal Society Open Science, 2022).

Medical applications:

My research also has applications in medicine, a recent example being a computational pipeline to assess cardiac dyssynchrony in patients with cardiomyopathies in collaboration with the British Hospital in Buenos Aires, Argentina (Fernandez et al, Scientific Reports, 2022). Molecular modelling from my laboratory has been instrumental in unravelling the core molecular mechanisms underlying immune responses in collaboration with Prof. Claudia Gunther and Prof. Min Ae Lee-Kirsch at the University Hospital Dresden, Germany (Berndt et al, J Invest Dermatol, 2022; König et al, Ann Rheum Dis, 2017; Günther et al, Journal of Clinical Investigation, 2015).

Current Lab members:

Dr. Alberto Ceccarelli, Postdoc

Augusto Borges, PhD student

Natalia G. Lavalle, PhD student

Hernan Arce, PhD student

Carla Soprano, PhD student

Rodrigo Cordoba, Diploma student

Nicolas Aldecoa, Diploma student

Irene Constantinidou, UG student

Mia Wong, UG student

Aitana Marzal Re, UG student

Firzanah Khaider, UG student

Mia Almendros, UG student

Mattie Williamson, UG student

Ex member of the lab:

Dr. Diego I. Cattoni (ex postdoc)

Dr. H. Ariel Alvarez (ex postdoc)

Dr. Juan Fernandez (ex postdoc)

Dr. Emanuel Cura Costa (ex postdoc and PhD student)

Dr. Fabian Rost (ex PhD student)

Alberto Ceccarelli (ex PhD student and Diploma student)

Valeria Caliaro (ex PhD student)

Augusto Borges (ex Diploma student)

Natalia G. Lavalle (ex Diploma student)

Lisandro Milocco (ex Diploma student)

Valeria Blanco (ex Diploma student)

Allison Courage (ex Master student)

Rebecca Beagle (ex Master student)

James Kwabena Owusu (ex Master student)

Yixuan Wang (ex Master student)

Samuel Atkins (ex Master student)

Ben Clarke (ex Master student)

Sofia Birgani (ex UG student)

Ella Wragg (ex UG student)

Jennifer Monk (ex UG student)

Kenzia Fernandes (ex UG student)

Muhammad Rajah (ex UG student)

School of Biosciences

University of Nottingham
Sutton Bonington Campus
Nr Loughborough
LE12 5RD, UK

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