Projects
Ankyrin-1 complex
The ankyrin-1 complex is essential for maintaining the characteristic biconcave disc shape of erythrocytes and the exceptional deformability and gas exchange properties of the erythrocyte membrane. It achieves this by tethering the spectrin-actin cytoskeleton to the red blood cell membrane, and acting as a metabolic hub that connects membrane proteins involved in gas exchange, pH control, and regulation of cellular volume and deformability. Our structure (Vallese et al. 2022) of the ankyrin-1 complex has provided critical insights into the molecular mechanism by which ankyrin mediates membrane protein organization, but fundamental questions remain unanswered. For example, how do the specific protein-protein interactions that occur within the ankyrin-1 complex contribute to its function?
To answer to these questions, in my laboratory, I will expand on my initial structural investigations to obtain a comprehensive understanding of ankyrin complex architecture, dynamics, and regulation. I will employ a combination of structural and functional approaches to explore both the role of the ankyrin-1 complex in the erythrocyte’s membrane curvature and its function as a metabolic hub involved in the diffusion of CO2 across the membrane.
Cardiomyocytes ankyrin complexes
Cardiomyocytes are the fundamental contractile cells in the heart and proper rhythmic contractions require finely tuned control of ion fluxes and calcium homeostasis. Ankyrin complexes are involved in several critical cardiac functions and thus hold the potential to play pivotal roles in cardiomyocyte health and contractile efficiency. Exploring the structure and function of ankyrin complexes within cardiomyocytes is crucial not only for understanding their role in cardiac physiology, but also for gaining insights into their implications for therapeutic advancements.
Several questions come to mind when considering these goals: What is the precise composition of the ankyrin complexes in cardiomyocytes? How do the ankyrin-2 and ankyrin-3 complexes contribute to cardiac membrane organization and integrity? How are these complexes regulated in response to physiological and pathological stimuli in the heart? And finally, can modulating the ankyrin-2 complex be a potential therapeutic strategy for heart diseases? The Lab will adopt a multidisciplinary approach to address these questions.
