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)

Recent Publications

  • CECCARELLI, ALBERTO S., BORGES, AUGUSTO and CHARA, OSVALDO, 2022. Size matters: tissue size as a marker for a transition between reaction–diffusion regimes in spatio-temporal distribution of morphogens Royal Society Open Science. 9(1), 211112
  • RIQUELME-GUZMÁN, CAMILO, SCHUEZ, MARITTA, BÖHM, ALEXANDER, KNAPP, DUNJA, EDWARDS-JORQUERA, SANDRA, CECCARELLI, ALBERTO S., CHARA, OSVALDO, RAUNER, MARTINA and SANDOVAL-GUZMÁN, TATIANA, 2022. Postembryonic development and aging of the appendicular skeleton in Ambystoma mexicanum Developmental Dynamics. 251(6), 1015-1034
  • OLIVEIRA, CATARINA R, KNAPP, DUNJA, ELEWA, AHMED, GERBER, TOBIAS, GONZALEZ MALAGON, SANDRA G, GATES, PHILLIP B, WALTERS, HANNAH E, PETZOLD, ANDREAS, ARCE, HERNAN, CORDOBA, RODRIGO C and OTHERS, 2022. Tig1 regulates proximo-distal identity during salamander limb regeneration Nature communications. 13(1), 1-16
  • JUAN M. F. FERN'ANDEZ, DAMI'AN N. SPAGNUOLO, MAR'IA T. POLITI, IV'AN A. TELLO SANTACRUZ, MIGUEL SCHIAVONE, C'ESAR C'ACERES MONI'E, HORACIO A. AVACA and OSVALDO CHARA, 2022. Vectorcardiography-derived index allows a robust quantification of ventricular electrical synchrony Scientific Reports. 12(1),
  • BERNDT, NICOLE, WOLF, CHRISTINE, FISCHER, KRISTINA, COSTA, EMANUEL CURA, KNUSCHKE, PETER, ZIMMERMANN, NICK, SCHMIDT, FRANZISKA, MERKEL, MARTIN, CHARA, OSVALDO, LEE-KIRSCH, MIN AE and OTHERS, 2022. Photosensitivity and cGAS-Dependent IFN-1 Activation in Patients with Lupus and TREX1 Deficiency Journal of Investigative Dermatology. 142(3), 633-640
  • CURA COSTA, EMANUEL, OTSUKI, LEO, RODRIGO ALBORS, AIDA, TANAKA, ELLY M and CHARA, OSVALDO, 2021. Spatiotemporal control of cell cycle acceleration during axolotl spinal cord regeneration eLife. 10, e55665
  • MUÑOZ-NAVA, LUIS MANUEL, ALVAREZ, HUGO ARIEL, FLORES-FLORES, MARYCRUZ, CHARA, OSVALDO and NAHMAD, MARCOS, 2020. A dynamic cell recruitment process drives growth of the Drosophila wing by overscaling the vestigial expression pattern Developmental biology. 462(2), 141-151
  • MEDELNIK, JAN-PHILIP, ROENSCH, KATHLEEN, OKAWA, SATOSHI, DEL SOL, ANTONIO, CHARA, OSVALDO, MCHEDLISHVILI, LEVAN and TANAKA, ELLY M, 2018. Signaling-dependent control of apical membrane size and self-renewal in rosette-stage human neuroepithelial stem cells Stem cell reports. 10(6), 1751-1765
  • CHARA, OSVALDO, BORGES, AUGUSTO, MILHIET, PIERRE-EMMANUEL, NÖLLMANN, MARCELO and CATTONI, DIEGO I, 2018. Sequence-dependent catalytic regulation of the SpoIIIE motor activity ensures directionality of DNA translocation Scientific reports. 8(1), 1-10
  • KÖNIG, NADJA, FIEHN, CHRISTOPH, WOLF, CHRISTINE, SCHUSTER, MAX, COSTA, EMANUEL CURA, TÜNGLER, VICTORIA, ALVAREZ, HUGO ARIEL, CHARA, OSVALDO, ENGEL, KERSTIN, GOLDBACH-MANSKY, RAPHAELA and OTHERS, 2017. Familial chilblain lupus due to a gain-of-function mutation in STING Annals of the rheumatic diseases. 76(2), 468-472
  • ROST, FABIAN, ALBORS, AIDA RODRIGO, MAZUROV, VLADIMIR, BRUSCH, LUTZ, DEUTSCH, ANDREAS, TANAKA, ELLY M and CHARA, OSVALDO, 2016. Accelerated cell divisions drive the outgrowth of the regenerating spinal cord in axolotls Elife. 5,
  • CURRIE, JOSHUA D, KAWAGUCHI, AKANE, TRASPAS, RICARDO MORENO, SCHUEZ, MARITTA, CHARA, OSVALDO and TANAKA, ELLY M, 2016. Live imaging of axolotl digit regeneration reveals spatiotemporal choreography of diverse connective tissue progenitor pools Developmental cell. 39(4), 411-423
  • VITALI, VICTORIA, SUTKA, MOIRA, AMODEO, GABRIELA, CHARA, OSVALDO and OZU, MARCELO, 2016. The water to solute permeability ratio governs the osmotic volume dynamics in beetroot vacuoles Frontiers in plant science. 7, 1388
  • LEAL DENIS, M FLORENCIA, ALVAREZ, H ARIEL, LAURI, NATALIA, ALVAREZ, CORA L, CHARA, OSVALDO and SCHWARZBAUM, PABLO J, 2016. Dynamic regulation of cell volume and extracellular ATP of human erythrocytes PloS one. 11(6), e0158305
  • CATTONI, DIEGO I, CHARA, OSVALDO, KAUFMAN, SERGIO B and GONZÁLEZ FLECHA, F LUIS, 2015. Cooperativity in binding processes: New insights from phenomenological modeling PloS one. 10(12), e0146043
  • ALBORS, AIDA RODRIGO, TAZAKI, AKIRA, ROST, FABIAN, NOWOSHILOW, SERGEJ, CHARA, OSVALDO and TANAKA, ELLY M, 2015. Planar cell polarity-mediated induction of neural stem cell expansion during axolotl spinal cord regeneration elife. 4, e10230
  • CHARA, OSVALDO and BRUSCH, LUTZ, 2015. Mathematical modelling of fluid transport and its regulation at multiple scales Biosystems. 130, 1-10
  • GÜNTHER, CLAUDIA, KIND, BARBARA, REIJNS, MARTIN AM, BERNDT, NICOLE, MARTINEZ-BUENO, MANUEL, WOLF, CHRISTINE, TÜNGLER, VICTORIA, CHARA, OSVALDO, LEE, YOUNG AE, HÜBNER, NORBERT and OTHERS, 2015. Defective removal of ribonucleotides from DNA promotes systemic autoimmunity The Journal of clinical investigation. 125(1), 413-424
  • CHARA, OSVALDO, TANAKA, ELLY M and BRUSCH, LUTZ, 2014. Mathematical modeling of regenerative processes Current Topics in Developmental Biology. 108, 283-317
  • BLANCO, MARÍA VALERIA, CATTONI, DIEGO IGNACIO, CARRIQUIRIBORDE, PEDRO, GRIGERA, JOSÉ RAÚL and CHARA, OSVALDO, 2014. Kinetics of bioaccumulation of heavy metals in Odontesthes bonariensis is explained by a single and common mechanism Ecological modelling. 274, 50-56
  • ROENSCH, KATHLEEN, TAZAKI, AKIRA, CHARA, OSVALDO and TANAKA, ELLY M, 2013. Progressive specification rather than intercalation of segments during limb regeneration Science. 342(6164), 1375-1379
  • CATTONI, DIEGO I, CHARA, OSVALDO, GODEFROY, CÉDRIC, MARGEAT, EMMANUEL, TRIGUEROS, SONIA, MILHIET, PIERRE-EMMANUEL and NÖLLMANN, MARCELO, 2013. SpoIIIE mechanism of directional translocation involves target search coupled to sequence-dependent motor stimulation EMBO reports. 14(5), 473-479
  • TÜNGLER, VICTORIA, STAROSKE, WOLFGANG, KIND, BARBARA, DOBRICK, MANUELA, KRETSCHMER, STEFANIE, SCHMIDT, FRANZISKA, KRUG, CLAUDIA, LORENZ, MIKE, CHARA, OSVALDO, SCHWILLE, PETRA and OTHERS, 2013. Single-stranded nucleic acids promote SAMHD1 complex formation Journal of molecular medicine. 91(6), 759-770
  • OZU, MARCELO, ALVAREZ, H ARIEL, MCCARTHY, ANDRÉS N, GRIGERA, J RAÚL and CHARA, OSVALDO, 2013. Molecular dynamics of water in the neighborhood of aquaporins European Biophysics Journal. 42(4), 223-239
  • LUKSCH, HELLA, ROMANOWSKI, MICHAEL J, CHARA, OSVALDO, TÜNGLER, VICTORIA, CAFFARENA, ERNESTO R, HEYMANN, MICHAEL C, LOHSE, PETER, AKSENTIJEVICH, IVONA, REMMERS, ELAINE F, FLECKS, SILVANA and OTHERS, 2013. Naturally Occurring Genetic Variants of Human Caspase-1 Differ Considerably in Structure and the Ability to Activate Interleukin-1$beta$ Human mutation. 34(1), 122-131
  • BRUSCA, MARIA I, IRASTORZA, RAMIRO M, CATTONI, DIEGO I, OZU, MARCELO and CHARA, OSVALDO, 2013. Mechanisms of interaction between Candida albicans and Streptococcus mutans: an experimental and mathematical modelling study Acta Odontologica Scandinavica. 71(3-4), 416-423
  • FERRARA, C GASTÓN, CHARA, OSVALDO and GRIGERA, J RAÚL, 2012. Aggregation of non-polar solutes in water at different pressures and temperatures: The role of hydrophobic interaction The Journal of chemical physics. 137(13), 135104
  • ALLEVA, KARINA, CHARA, OSVALDO and AMODEO, GABRIELA, 2012. Aquaporins: another piece in the osmotic puzzle FEBS letters. 586(19), 2991-2999
  • CATTONI, DIEGO I, RAVAZZOLA, CONSTANZA, TÜNGLER, VICTORIA, WAINSTEIN, DANIEL E and CHARA, OSVALDO, 2011. Effect of intestinal pressure on fistula closure during vacuum assisted treatment: a computational approach International Journal of Surgery. 9(8), 662-668
  • CHARA, OSVALDO, ESPELT, MARÍA V, KRUMSCHNABEL, GERHARD and SCHWARZBAUM, PABLO J, 2011. Regulatory volume decrease and P receptor signaling in fish cells: mechanisms, physiology, and modeling approaches Journal of Experimental Zoology Part A: Ecological Genetics and Physiology. 315(4), 175-202
  • WAINSTEIN, DANIEL E, TÜNGLER, VICTORIA, RAVAZZOLA, CONSTANZA and CHARA, OSVALDO, 2011. Management of external small bowel fistulae: challenges and controversies confronting the general surgeon International Journal of Surgery. 9(3), 198-203
  • CHARA, OSVALDO, MCCARTHY, ANDRÉS N and GRIGERA, J RAÚL, 2011. Crossover between tetrahedral and hexagonal structures in liquid water Physics Letters A. 375(3), 572-576
  • CHARA, OSVALDO, PAFUNDO, DIEGO E and SCHWARZBAUM, PABLO J, 2010. Negative feedback of extracellular ADP on ATP release in goldfish hepatocytes: a theoretical study Journal of theoretical biology. 264(4), 1147-1158
  • CHARA, OSVALDO, PAFUNDO, DIEGO E and SCHWARZBAUM, PABLO J, 2009. Kinetics of extracellular ATP from goldfish hepatocytes: a lesson from mathematical modeling Bulletin of mathematical biology. 71(5), 1025-1047
  • ALLEVA, KARINA, CHARA, OSVALDO, SUTKA, MOIRA R and AMODEO, GABRIELA, 2009. Analysis of the source of heterogeneity in the osmotic response of plant membrane vesicles European Biophysics Journal. 38(2), 175-184
  • CHARA, OSVALDO, MCCARTHY, ANDRÉS N, FERRARA, C GASTÓN, CAFFARENA, ERNESTO R and GRIGERA, J RAÚL, 2009. Water behavior in the neighborhood of hydrophilic and hydrophobic membranes: lessons from molecular dynamics simulations Physica A: Statistical Mechanics and its Applications. 388(21), 4551-4559
  • PAFUNDO, DIEGO E, CHARA, OSVALDO, FAILLACE, MARÍA P, KRUMSCHNABEL, GERHARD and SCHWARZBAUM, PABLO J, 2008. Kinetics of ATP release and cell volume regulation of hyposmotically challenged goldfish hepatocytes American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 294(1), R220-R233
  • WAINSTEIN, DANIEL EDGARDO, FERNANDEZ, ERNESTO, GONZALEZ, DANIEL, CHARA, OSVALDO and BERKOWSKI, DARIO, 2008. Treatment of high-output enterocutaneous fistulas with a vacuum-compaction device. A ten-year experience World journal of surgery. 32(3), 430-435
  • CATTONI, DI and CHARA, O, 2008. Vacuum effects over the closing of enterocutaneous fistulae: a mathematical modeling approach Bulletin of Mathematical Biology. 70(1), 281-296
  • CHARA, OSVALDO, GRIGERA, JOSÉ RAÚL and MCCARTHY, ANDRÉS N, 2007. Studying the unfolding kinetics of proteins under pressure using long molecular dynamic simulation runs Journal of biological physics. 33(5), 515-522
  • BRUSCA, MI, CHARA, O, STERIN-BORDA, L and ROSA, AC, 2007. Influence of different orthodontic brackets on adherence of microorganisms in vitro The Angle Orthodontist. 77(2), 331-336
  • CHARA, O, FORD, P, RIVAROLA, V, PARISI, M and CAPURRO, C, 2005. Asymmetry in the osmotic response of a rat cortical collecting duct cell line: role of aquaporin-2 The Journal of membrane biology. 207(3), 143-150
  • RIVAROLA, VALERIA, FORD, PAULA, CHARA, OSVALDO, PARISI, MARIO and CAPURRO, CLAUDIA, 2005. Functional and Molecular Adaptation of Cl-/HCO3-Exchanger to Chronic Alkaline Media in RenalCells Cellular Physiology and Biochemistry. 16(4-6), 271-280
  • FORD, PAULA, RIVAROLA, VALERIA, CHARA, OSVALDO, BLOT-CHABAUD, MARCEL, CLUZEAUD, FRANÇOISE, FARMAN, NICOLETTE, PARISI, MARIO and CAPURRO, CLAUDIA, 2005. Volume regulation in cortical collecting duct cells: role of AQP2 Biology of the Cell. 97(9), 687-697
  • FORD, P, RIVAROLA, V, KIERBEL, A, CHARA, O, BLOT-CHABAUD, M, FARMAN, N, PARISI, M and CAPURRO, C, 2002. Differential role of Na+/H+ exchange isoforms NHE-1 and NHE-2 in a rat cortical collecting duct cell line The Journal of membrane biology. 190(2), 117-125

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