Karl Schlögl-Preis 2021

Monica L. Fernández-Quintero wird für ihre Dissertation The Dynamic Nature of Antigen Receptors ausgezeichnet.

The main focus of the submitted thesis The Dynamic Nature of Antigen Receptors are antibodies and the question of how different antibody conformations affect the binding behavior. The scientific and economic interest in antibodies has multiplied in recent years. Antibodies are characterized by their unique binding properties and their broad applicability. In particular, therapeutic antibodies have revolutionized the treatment of numerous life-threatening diseases that severely limit quality of life, such as cancer or autoimmune diseases.

In her dissertation, Monica L. Fernández-Quintero succeeded in fundamentally re-examining the binding behavior of antibodies. She developed methods that can substantially improve and simplify antibody design and structure prediction. Description of the binding properties and characterizing the antigen-binding site is essential for understanding the function of the antibody. She and her team showed that the CDR loops are not confined to static canonical conformations but rather exist as conformational ensembles. The analysis of these conformational ensembles revealed, that in many cases, the antigen binding competent conformation is the dominant conformation in solution and the available antigen-binding fragment X-ray structures very frequently are strongly distorted by crystal contacts. Thus, she strongly suggests that the flexibility of the antigen-binding site should be considered when designing and optimizing therapeutic antibodies.

Furthermore, antibodies can rapidly evolve and adapt in specific response to antigens. During the affinity maturation process the immune system produces antibodies with higher specificity and affinity through various rounds of somatic hypermutations in response to an antigen. Elucidating the affinity maturation process is fundamental for understanding immunity and for the development of biotherapeutics. Therefore, she and other group members analyzed pairs of antibody fragments differing in their specificity and in distinct stages of affinity maturation. Monica L. Fernández-Quintero consistently found that affinity maturation is accompanied by a decrease of global and local flexibility, reflected in a substantial reduction of conformational diversity.

The results do not only elucidate a key aspect in biomolecular protein-protein recognition, but also have broad implications in the field of antibody structure design and engineering and will lead to a paradigm change for antibody CDR loop structures. In addition, the methods Monica L. Fernández-Quintero developed, provide innovative approaches that make the design and development of antibodies more efficient and thus enable faster treatment of patients.

Die Preisträgerin

Monica L. Fernández-Quintero hat die Bachelor-und Master-Studien an der Universität Innsbruck abgeschlossen (2017/2018). Sie promovierte im Fach Chemie an der Innsbrucker Universität (2020). Derzeit absolviert Monica L. Fernández-Quintero die PhD-Programme „Molecular and Cellular Biology of Diseases (MCBD)“ und „Calcium Channels in Excitable Cells (CavX)“an der Medizinischen Universität Innsbruck; Schwerpunkt ihrer Forschungen sind Kalziumkänale. Im Rahmen dieses Programms ist sie als Forschungs- und Universitäts-Assistentin tätig. Seit September 2020 ist Monica L. Fernández-Quintero post doc-Universitätsassistentin am Center for Molecular Biosciences der Universität Innsbruck. Im April 2022 erhielt Monica L. Fernández-Quintero ein APART-MINT-Stipendium der ÖAW.