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Sasha DE HENAU
April 15 at 09:30 - 11:00
From University Medical Center, Utrecht (NLD)
will give a seminar entitled :
Seeing is Believing – Visualizing the Fundamental Role of Hydrogen Peroxide Signaling in Biology
Hydrogen peroxide (H2O2) is a major second messenger in cell biology, regulating normal development, morphogenesis, disease progression and ageing. However, because of the extremely challenging nature of measuring H2O2 changes in vivo and on a subcellular level, we know very little of the dynamics of the H2O2 signaling pathways themselves or how H2O2 can modulate biological processes with high specificity.
I developed a pioneering model based on cell polarization of the C. elegans zygote, which requires tight regulation of signaling cascades in both time and space, to start characterizing the regulatory mechanisms in H2O2 signaling. Live imaging and modulation of subcellular H2O2 levels in this system revealed that mitochondria, a main source of cellular H2O2, promote polarization by increasing local H2O2 levels. Using optogenetics to locally recruit mitochondria to the cell membrane further showed that mitochondrial H2O2 by itself is sufficient to induce polarization. Overall, this research described two mechanisms by which mitochondria can initiate H2O2 signaling and led to the surprising discovery that mitochondrial H2O2 is an initiating factor in cell polarization, opening up new research avenues in this field.
In my follow up studies, I aim to characterize H2O2 signaling from the molecular to the tissue level using the C. elegans reproductive system as model tissue. I will present a high-content screening approach to address the dynamics and biological impact of H2O2 signaling pathways across all major cellular compartments. In addition, I will explain how case studies of mitochondrial H2O2 signaling – during oocyte maturation and during actomyosin dynamics – can be used to further unravel how specificity in H2O2 signaling is achieved. The knowledge acquired with these studies will serve as framework to address the role of H2O2 signaling in other tissues and organisms, and will help explain how H2O2 changes during disease affect downstream biological processes.