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Subcellular calcium signalling microdomains regulating cardiomyocytes growth and function

Fiona DE MATOS

442
11
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专业摘要

I began my higher education with a Bachelor's degree in Science and Technology at the University of Tours, where I discovered and developed a passion for human physiology, pharmacology, and pathophysiology. After graduation, I pursued a Master’s degree in Pharmacology, Pathophysiology, and Physiology, which introduced me to electrophysiology and laboratory research and gave me the opportunity to complete two internships. The first internship, from April to June 2019, took place at the STIM laboratory in Poitiers within the C2M team. I worked on calcium signaling remodeling in uveal melanoma using a hepatic metastatic cell line. I modulated GNA11 protein/gene expression, involved in uveal melanoma, using siRNA transfection and pharmacological inhibitors. I then measured Store-Operated Calcium Entry (SOCE) and Constitutive Calcium Entry using spectrofluorimetric analysis. Additionally, I performed Western blotting to detect and quantify key proteins involved in calcium signaling, such as TRPC1, ORAI, and STIM1. The following year, I spent six months in Norway at the Department of Pharmacology to develop my adaptability, expand my professional network, improve my English, and gain deeper insight into pharmacology and new laboratory techniques. I focused on cardiac lipotoxicity, a process triggered by cardiovascular diseases, obesity, or diabetes. Using the H9C2 cell line treated with palmitic acid, I established a model of cardiac lipotoxicity and measured cell death via flow cytometry. I also tested drugs known to modulate signaling pathways that reduce cell death, including natriuretic peptides and cAMP-related pathways. My academic journey made me realize that I want to pursue research in physiology, particularly in cardiovascular diseases. That is why I applied for the PhD project proposed by Professor Roderick and Professor Rajagopal. This project perfectly combines my two previous internships, as it focuses on studying calcium signaling during cardiac aging and associated diseases, with a specific emphasis on inositol triphosphate (IP₃) receptors and their roles in different subcompartments of cardiomyocytes. During my PhD, I had the opportunity to spend a year in Australia collaborating with Professor Vijay Rajagopal. During this time, I worked with both small and large animal models, developed my skills in calcium imaging, and became fully independent in planning my research. I learned to ask strategic scientific questions, develop my own pipelines for calcium data analysis, and rationalize my results. I also learned to isolate cardiomyocytes from animal models such as rats and sheep, and had the unique opportunity to work with human heart biopsies. This experience significantly strengthened my analytical and experimental abilities while allowing me to contribute to high-level collaborative research.

技能

Cardiac research
Cardiac ageing
Calcium signalling
Inositol 1,4,5-Trisphosphate Receptors
Cardiac remodelling

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