Project acronym ANEUPLOIDY
Project Molecular origins of aneuploidies in healthy and diseased human tissues
Researcher (PI) Iva TOLIC, Angelika Amon, Geert Kops, Nenad Pavin
Host Institution (HI) RUDER BOSKOVIC INSTITUTE
Country Croatia
Call Details Synergy Grants (SyG), SyG, ERC-2019-SyG
Summary Chromosome segregation errors cause aneuploidy, a state of karyotype imbalance that accelerates tumor formation and impairs embryonic development. Even though mitotic errors have been studied extensively in cell cultures, the mechanisms generating various errors, their propagation and effects on genome integrity are not well understood. Moreover, very little is known about mitotic errors in complex tissues. The main goal of this project is to uncover the molecular origins of mitotic errors and their contribution to karyotype aberrations in healthy and diseased tissues. To achieve our goal, we have assembled an interdisciplinary team of experts in molecular and cell biology, cell biophysics, chromosomal instability in cancer, and theoretical physics. Our team will introduce novel approaches to study aneuploidy (superresolution microscopy, optogenetics, laser ablation, single cell karyotype sequencing) and apply them to state-of-the-art tissue cultures (mammalian organoids and tumoroids). In close collaboration, Tolić will establish assays to detect and quantify error types in cells, and Kops and Amon will use the assays on various healthy and cancer tissues. Tolić and Kops will uncover the molecular origins of errors, their propagation and impact on genome integrity, while Amon will lead the investigation of the mechanisms that ensure high chromosome segregation fidelity in healthy tissues. Interwoven in these collaborations are the efforts of Pavin, who will develop a theoretical model to describe the origin of errors and to quantitatively link chromosome segregation fidelity in single cells and tissues. Model and experiment will continuously inspire each other, to achieve deep understanding of how mitotic errors arise, how they propagate and how they impact on cell populations. Thus, the extensive sets of expertise present in our team will be combined and expanded with novel technologies to tackle the big challenge of the origins of aneuploidy in humans.
Summary
Chromosome segregation errors cause aneuploidy, a state of karyotype imbalance that accelerates tumor formation and impairs embryonic development. Even though mitotic errors have been studied extensively in cell cultures, the mechanisms generating various errors, their propagation and effects on genome integrity are not well understood. Moreover, very little is known about mitotic errors in complex tissues. The main goal of this project is to uncover the molecular origins of mitotic errors and their contribution to karyotype aberrations in healthy and diseased tissues. To achieve our goal, we have assembled an interdisciplinary team of experts in molecular and cell biology, cell biophysics, chromosomal instability in cancer, and theoretical physics. Our team will introduce novel approaches to study aneuploidy (superresolution microscopy, optogenetics, laser ablation, single cell karyotype sequencing) and apply them to state-of-the-art tissue cultures (mammalian organoids and tumoroids). In close collaboration, Tolić will establish assays to detect and quantify error types in cells, and Kops and Amon will use the assays on various healthy and cancer tissues. Tolić and Kops will uncover the molecular origins of errors, their propagation and impact on genome integrity, while Amon will lead the investigation of the mechanisms that ensure high chromosome segregation fidelity in healthy tissues. Interwoven in these collaborations are the efforts of Pavin, who will develop a theoretical model to describe the origin of errors and to quantitatively link chromosome segregation fidelity in single cells and tissues. Model and experiment will continuously inspire each other, to achieve deep understanding of how mitotic errors arise, how they propagate and how they impact on cell populations. Thus, the extensive sets of expertise present in our team will be combined and expanded with novel technologies to tackle the big challenge of the origins of aneuploidy in humans.
Max ERC Funding
9 999 750 €
Duration
Start date: 2020-04-01, End date: 2026-03-31
Project acronym DEEP PURPLE
Project DEEP PURPLE: darkening of the Greenland Ice Sheet
Researcher (PI) Martyn TRANTER, Alexandre Barbosa Anesio, Liane Benning
Host Institution (HI) AARHUS UNIVERSITET
Country Denmark
Call Details Synergy Grants (SyG), SyG, ERC-2019-SyG
Summary The stability of the Greenland Ice Sheet (GrIS) is a threat to coastal communities worldwide. The PIs have changed our understanding of why it darkens during the melt season, becoming increasingly deep purple due to pigmented ice algal blooms in the ice surface, producing more melt and accelerating the GrIS towards its tipping point, and increasing sea level. The next step jump in our understanding of biological darkening will be provided by DEEP PURPLE, which will establish the factors that control ice algal blooms. These factors are essential for modelling of future melting, which require a process-based understanding of blooming. DEEP PURPLE will quantify the synergies between the biology, chemistry and physics of ice algae micro-niches in rotting, melting ice, and examine the combination of factors which stabilise them. State-of-the-science analytical and observational methods will be employed to characterise the complex mosaic of wet ice habitats, dependent on factors such as the hydrology, nutrient status, particulate content and light fields within these continually evolving ice-water-particulate-microbe systems. We will quantitatively assess why and how the fine light mineral dust particulates contained within the melting ice amplify the growth of ice algae. The particulate content and composition of different layers in the GrIS is dependent on age, and so the algae that the melting ice can support may fundamentally change over time. We look back to understand if the ice biome has changed through the Anthropocene via analyse of fjord sediments. The first draft genome of ice algae will show their key adaptations to glacier surface habitats. DEEP PURPLE looks forward by providing the critical field data sets and conceptual models of ice algal growth that will facilitate the next generation of predictive models of sea level rise due to biologically enhanced melting of the GrIS.
Summary
The stability of the Greenland Ice Sheet (GrIS) is a threat to coastal communities worldwide. The PIs have changed our understanding of why it darkens during the melt season, becoming increasingly deep purple due to pigmented ice algal blooms in the ice surface, producing more melt and accelerating the GrIS towards its tipping point, and increasing sea level. The next step jump in our understanding of biological darkening will be provided by DEEP PURPLE, which will establish the factors that control ice algal blooms. These factors are essential for modelling of future melting, which require a process-based understanding of blooming. DEEP PURPLE will quantify the synergies between the biology, chemistry and physics of ice algae micro-niches in rotting, melting ice, and examine the combination of factors which stabilise them. State-of-the-science analytical and observational methods will be employed to characterise the complex mosaic of wet ice habitats, dependent on factors such as the hydrology, nutrient status, particulate content and light fields within these continually evolving ice-water-particulate-microbe systems. We will quantitatively assess why and how the fine light mineral dust particulates contained within the melting ice amplify the growth of ice algae. The particulate content and composition of different layers in the GrIS is dependent on age, and so the algae that the melting ice can support may fundamentally change over time. We look back to understand if the ice biome has changed through the Anthropocene via analyse of fjord sediments. The first draft genome of ice algae will show their key adaptations to glacier surface habitats. DEEP PURPLE looks forward by providing the critical field data sets and conceptual models of ice algal growth that will facilitate the next generation of predictive models of sea level rise due to biologically enhanced melting of the GrIS.
Max ERC Funding
11 007 344 €
Duration
Start date: 2020-01-01, End date: 2025-12-31
