From University Medical Center, Utrecht (NLD)

will give a seminar entitled :

Seeing is Believing – Visualizing the Fundamental Role of Hydrogen Peroxide Signaling in Biology

Abstract :

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.