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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 Universit盲t 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.
Here you can see (from the Future to the past) a list of projects we are investigating in our lab:
Proliferation-dependent regenerative response stops after cells "count" number of neighbors
We explored how to achieve organ-wide regeneration through locally controlled cell proliferation. This computational adventure in the addressed this problem in the neuromast within the zebrafish lateral line. In a collaboration with the lab of Hernan Lopez-Schier, we perfomed laser ablation of neuromasts, which resulted in an ordered proliferation-dependent regenerative response. We investigated the problem quantitatively by using Cellular Potts Model (CPM). Our results show that the tissue-wide regenerative response of the neuromast is consistent with a delayed proliferation switch modulated by the the number of neighbors. Feel free to check , and summaries of this study.
Plants use Physics principles to push through hard soil
In this study, published in , we have contributed to the understanding of how ethylene and cell wall mechanics in roots respond to soil compaction. This study was led by brilliant colleagues! Featuring Jiao Zhang, , , , Wanqi Zhang, the amazing Malcolm Bennett & more. A nice recap of the article can be found here in !
Computational inference of mechanical forces in tissues:
We have recently developed ForSys, a computational tool for dynamic inference of mechanical stresses in tissues (). A tutorial on how to use ForSys can be found and . Here you can find our recent review on computational tools of force inference ().
How cells know where they are and where to go during limb regeneration in the axolotl:
In this new study (), carried out in collaboration with Max Yun, now at the Chinese Institutes for Medical Research in Beijing, China, we combined experimental, computational, and theoretical approaches to understand how proximalisation occurs. We link this process, in which the positional identity of cells is altered, to the existence of a theoretical proximalisation potential. This potential gives rise to a proximalisation force that moves the cells during regeneration. In this article and in the previous one, my lab developed , a Python-based 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 ().
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 (). We also characterized the dorsal-ventral gene expression of the axolotl spinal cord during regeneration and development, in collaboration with the lab of Elly Tanaka (). 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 (). By combining mathematical modelling and image analysis, we were able to determine that axolotl spinal cord regeneration is primarily driven by cell cycle acceleration (; ).
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 M眉nchen (). 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 (). 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 (). Previously, I developed image analysis tools to identify the source of migrating progenitor cells in regenerating axolotl digits and limbs (). 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 ().
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 (). Previously, we determined the existence of a critical tissue size that separates two reaction-diffusion regimes of morphogen gradients ().
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 (). 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 (; ; ).
Current Lab members:
Dr. Alberto Ceccarelli, Postdoc
Hernan Arce, PhD student
Carla Soprano, PhD student
Ahmed Ramzy, PhD student
Rodrigo Cordoba, Associated researcher
Nicolas Aldecoa, Diploma student
Olamide Adenuga, Master student
Leah Ward, UG student
Wei-En Goh, UG student
Luke Drake, UG student
Ex members of the lab:
Dr. Diego I. Cattoni (ex postdoc)
Dr. H. Ariel Alvarez (ex postdoc)
Dr. Juan Fernandez (ex postdoc)
Natalia G. Lavalle (ex PhD student and Diploma student)
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)
Wenting Lei (ex Master student)
Jiayu Zhang (ex Master student)
Tong Wu (ex Master 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)
Irene Constantinidou (ex UG student)
Mia Wong (ex UG student)
Aitana Marzal Re (ex UG student)
Firzanah Khaider (ex UG student)
Mia Almendros (ex UG student)
Mattie Williamson (ex UG 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)