research groups

Cellular-Structural Biology Lab

summary

The structure and function of proteins depend on multiple factors such as sub-celullar localization, post-translational modifications and interactions with other biomolecules. However, most protein structural and mechanistic studies are typically performed on isolated samples, under conditions that differ substantially from in vivo environments of live cells. In our group we use NMR in live cells and multicellular organisms to obtain structural and functional information of proteins in their native environments and to study how oxidative post-translational modifications modulate central physiological and pathological processes involved in cardiovascular and neurodegenerative disorders.
GROUP DIRECTOR
Binolfi, Andrés

Sede:

CCT

Email:

binolfi@ibr-conicet.gov.ar
Project Directors
Associated researchers
  • Lombardo, Veronica
PhD POST-Fellows
PhD Fellows
  • Guastaferri, Florencia
  • Herrera Estrada, Idalia
Undergraduate Students
  • Piatti, Tomás
technicians

RESEARCH LINES

Oxidative stress and heart development

A large number of congenital heart defects (CHD) arise as a consequence of the interaction between environmental factors, infections and genetic susceptibilities. Imbalances in oxidative regulation mechanisms result in cardiac pathologies. Exposure to oxidative stress during pregnancy has been linked with CHD and a detailed knowledge of its effects on cardiac development at the morphological, molecular and cellular level constitutes the basis for the development of early detection methods and the design of novel therapeutic strategies. In this research line, headed by Dr Verónica Lombardo, we use high resolution microscopy, molecular and cell biology and NMR methodologies in zebrafish (Danio rerio) embryos to understand how oxidative stress impacts on cardiac morphogenesis and elucidate the redox signaling pathways involved in the development of congenital heart defects.

Oxidative stress, lipids and oxidative protein modifications

The increase in reactive oxygen species and the decline of enzymatic redox protective systems have been identified as risk factors for the development of neurodegenerative and cardiovascular diseases. They elicit multiple effects including protein oxidative modifications interfering with normal function and changes in the lipid composition of cell membranes, which introduce cellular stress and metabolic imbalances that promote pathological states. In a collaborative effort between our group and the group of Dr. Diego de Mendoza, we analyze the role of oxidative stress and the metabolism of unsaturated fatty acids and cholesterol in the cellular aggregation of amyloid proteins and other pathological processes. We use NMR methodologies in vitro, e in vivo, in Caenorhabditis elegans and in zebrafish, combined with protein biochemistry, microscopy and metabolomics approaches. Our initiative seeks to obtain a comprehensive high resolution picture of the effect of oxidative stress on cellular pathologies.

Images of our research lines

PUBLICATIONS AND PATENTS

Megadalton-sized dityrosine aggregates of α-Synuclein retain high degrees of structural disorder and internal dynamics.

Mol. Biol. 432, 166689, Verzini S., Shah M., Theillet F.X., Belsom A., Bieschke J., Wanker E.E., Rappsilber J., Binolfi A., Selenko P. (2020).

Megadalton-sized dityrosine aggregates of α-Synuclein retain high degrees of structural disorder and internal dynamics.

Mol. Biol. 432, 166689, Verzini S., Shah M., Theillet F.X., Belsom A., Bieschke J., Wanker E.E., Rappsilber J., Binolfi A., Selenko P. (2020).
DOI

An NMR-based biosensor to measure stereo-specific methionine sulfoxide reductase (MSR) activities in vitro and in vivo

Eur. J. 26, 14838. Sánchez-López C., Labadie N.,  Lombardo V.A.,  Biglione F.A.,  Manta B., Jacob R., Gladyshev V., Abdelilah-Seyfried S., Selenko P., Binolfi A. (2020).

An NMR-based biosensor to measure stereo-specific methionine sulfoxide reductase (MSR) activities in vitro and in vivo

Eur. J. 26, 14838. Sánchez-López C., Labadie N.,  Lombardo V.A.,  Biglione F.A.,  Manta B., Jacob R., Gladyshev V., Abdelilah-Seyfried S., Selenko P., Binolfi A. (2020).
DOI

Morphogenetic control of zebrafish cardiac looping by Bmp signaling.

Development, 146, 180091. Lombardo  A., Heise M., Moghtadaei M., Bornhorst D., Männer J., Abdelilah-Seyfried S. (2019).

Morphogenetic control of zebrafish cardiac looping by Bmp signaling.

Development, 146, 180091. Lombardo  A., Heise M., Moghtadaei M., Bornhorst D., Männer J., Abdelilah-Seyfried S. (2019).
DOI

Time-resolved NMR analysis of proteolytic α-synuclein processing in vitro and in cellulo.

Proteomics, 18, 1800056. Limatola A., Eichmann C., Jacob R., Ben-Nissan G., Sharon M., Binolfi A., Selenko P. (2018).

Time-resolved NMR analysis of proteolytic α-synuclein processing in vitro and in cellulo.

Proteomics, 18, 1800056. Limatola A., Eichmann C., Jacob R., Ben-Nissan G., Sharon M., Binolfi A., Selenko P. (2018).
DOI

Structural disorder of monomeric α-synuclein persists in mammalian cells.

Nature 530, 45. Theillet F-X, Binolfi A., Bekei B., Martorana A., Rose H. M., Stuiver M., Verzini S., Lorenz D., van Rossum M., Goldfarb D., Selenko P. (2016).

Structural disorder of monomeric α-synuclein persists in mammalian cells.

Nature 530, 45. Theillet F-X, Binolfi A., Bekei B., Martorana A., Rose H. M., Stuiver M., Verzini S., Lorenz D., van Rossum M., Goldfarb D., Selenko P. (2016).
DOI

contacto@conicet.gov.ar

Sede CCT Rosario

Ocampo y Esmeralda, Predio CONICET-Rosario
2000 Rosario, Santa Fe, Argentina
Tel. 54-341-4237070 / 4237500 / 4237200

Sede Facultad de Ciencias Bioquímicas y Farmacéuticas

Universidad Nacional de Rosario - Suipacha 531
2000 Rosario, Santa Fe, Argentina
Tel. +54 341 4350596 / 4350661 / 4351235

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