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Supramolecular Medicine !


Basic Research for Health Solutions

Supramolecular Medicine is devoted to translational research by combining interdisciplinary basic research to bring health solutions. The final goal is the promotion of quality-of-life and society well-being.

Translation requires a bi-directional effort starting from the identification of societal needs and ending with the development of technology/products to be brought back into society.

In general, chemists can establish connections between molecular information and biological function or dysfunction. However, molecular structure alone does not drive function; recognition and organization in both time and space are necessary. Biology can be better understood by considering it as ensembles of (bio-)molecules that exert tailored functions through molecular recognition and self-organization or self-assembly. The concept of ensembles of molecules to make a function is the core of supramolecular chemistry, an area of chemistry devoted to going beyond the molecule. Hence, Supramolecular Medicine is dedicated to providing a supramolecular understanding of biological processes for the development of preventive, diagnostic, and therapeutic strategies to tackle diseases and maintain health.

RESEARCH

Our research focuses on the design, synthesis, and evaluation of supramolecular systems based on small molecules and peptides that operate under aqueous conditions. We employ different tools from organic chemistry, biophysics, and cell biology at different levels of complexity.

The final aim is to obtain a profound understanding of the relationship between molecular structure, morphology, and function in a biologically relevant environment.

Nowadays, our principal research is directed towards understanding the mechanism of peptide/protein self-assembly and its roles on the delicate balance between health and disease in gluten-related disorders. From our investigations, it is clear that gluten peptides are not only pathogenic for celiac patients. They possess interesting molecular and supramolecular features that could be used to disclose the mechanism of cellular uptake and be translated into other pathologies like aggregopathies and even cancer. This translational research is complemented with other more basic projects in the area of protein/peptide-protein interaction, and functional molecules like photoswitchable biosystems.

Gluten related-disorders and Protein-Protein Interaction

Gluten-related disorders are a group of diseases that involve the activation of the immune system triggered by the ingestion of gluten. These disorders have a high prevalence in Western societies around 5% worldwide because gluten is present in wheat, rye, barley, and some varieties of oats.

It is accepted that the incomplete proteolysis of the gluten proteins is responsible for disease in susceptible individuals. From the chemical perspective, up to now, the research efforts focused on the identification, quantification, and separation of the components of gluten and connecting them with their pathological role in vitro and in vivo. Interestingly, while the primary structure of the molecules involved in the disease is known, there is a lack of information about their intrinsic behavior –such as their folding and molecular organization- under physiologically relevant conditions.

Gliadin and its 33-mer fragment have a central pathogenic role in the context of gluten-related. The aim of the present project is to elucidate the molecular, structural, and supramolecular basis of 33-mer oligomerization and the role of the 33-mer nanostructures in the delicate balance between health and disease.

Oligomerization and conformational transition, towards the β- parallel structure, are hallmarks of Alzheimer’s disease, Parkinson’s disease, and prion disease.

Based on these similarities, the relationship between 33-mer accumulations, due to proteolytical resistance, followed by oligomerization can be the up to now unknown trigger of disease before the onset of inflammation. This hypothesis opens new avenues to understand and treat this common pathology.

To prove this hypothesis, we moved from chemical and biophysics to immunological research, reporting for the first time that only large structures of 33-mer induce an innate immune response in macrophages which is mediated by Toll-like receptor (TLR) 4 activation. This result opens the understanding of the early stages of the disease. It connects activation of the innate immune system triggered by the presence of 33-mer protofilaments for the first time.

The current project combines different chemical and biological methodologies and approaches by including peptide chemistry, structural and supramolecular characterization methods, cellular biology approaches, proteomics, and super-resolution optical microscopy. By combining my research expertise and those of my collaborators, it will be possible to quantify and understand the role of the 33-mer oligomers as modulators of disease.

Our findings will open new avenues in the understanding of gluten-related disorders directed towards the design of new therapeutic targets beyond the gluten-free diet.

Funding: Deutsche Forschungsgemeinschaft (DFG)



Veronica Dodero

2003 Doctoral Thesis in Organic Chemistry. Supervised by Prof. J. C. Podesta (Universidad del Sur, Argentina) and Prof. T. Mitchell (University of Dortmund, Germany)

1998 Licenciado in Chemistry (BSc. Major). Universidad del Sur, Argentina

Since 2019 Principal Investigator, Faculty of Chemistry, OCIII, University of Bielefeld, Germany

2018 Guest Researcher in Prof N. Sewald’s group, University of Bielefeld, Germany

2015-2018 Georg Forster Fellow, Alexander von Humboldt Foundation (AvH)-HERMES, Faculty of Chemistry, Bielefeld University, Germany

2009-2015 Adjunct Professor of Organic Chemistry, Department of Chemistry, Universidad del Sur (UNS), Argentina

2008-2015 Adjunct Researcher, Organic Chemistry and Biomolecular Interactions, CONICET Argentina

2007-2007 Postdoctoral Researcher in Medicinal Chemistry with M. L. López Rodríguez, Complutense University of Madrid, Spain

2003-2007 Postdoctoral Researcher in Chemical Biology with J.L Mascareñas, University of Santiago de Compostela, Spain

2001-2002 Staff Assistant, Dortmund University, Germany

1998-2009 Staff Assistant in Organic Chemistry, UNS, Argentina

2018 Board Member Marie Curie Alumni Association German Chapter

2018 Visiting Professor, University of Seville, Faculty of Pharmacy, Spain

2015 Georg Forster Fellowship for Experienced Scientists-HERMES, Alexander von Humboldt Foundation

2010 DAAD Visiting Researcher, Bielefeld University, Germany.

2004 Fellowship of the Galician Government, University of Santiago de Compostela, Spain.

2004 Aaron and Fanny Fidelef de Nijamkim’s Award, UNS Best PhD student in Chemistry Year 2003, Argentina.

2000 DAAD fellowship, University of Dortmund, Germany

1998 CONICET fellowship, Argentina.

1998 Intercampus fellowship, University of Girona, Spain

1996 Universidad del Sur Research Student fellowship, Argentina

54+

Publications

950K

Finished Projects

2+

Awards Winning

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