Project acronym InPhoTime
Project Insect Photoperiodic Timer
Researcher (PI) David DOLEZEL
Host Institution (HI) Biologicke centrum AV CR, v. v. i.
Call Details Consolidator Grant (CoG), LS3, ERC-2016-COG
Summary Daylength measuring devices such as the photoperiodic timer enable animals to anticipate and thus survive adverse seasons. This ability has contributed to the great success of insects living in temperate regions. Yet the basis of photoperiodic sensing remains elusive, because of the lack of suitable genetic models expressing photoperiod-dependent seasonal phenotypes. We have developed the linden bug, Pyrrhocoris apterus, into a genetically tractable model with a robust, photoperiod-dependent reproductive arrest (diapause). With the available tools, this insect has become ideal for deciphering the regulation of seasonality. The project has 3 clear and ambitious objectives: 1). Our goal is to define the molecular and anatomical bases of the photoperiodic timer. To achieve this, we propose to identify photoperiodic timer genes, genes regulating input to the timer, and early output markers, through an RNA interference screen(s). To define the molecular mechanism of the timer, we will employ genome editing to precisely alter properties of the key players. 2). Next, we will combine techniques of neuronal backfilling, in-vivo fluorescent reporters, and microsurgery to define the photoperiodic timer anatomically and to examine its spatial relationship to the circadian clock in the insect brain. 3). We will exploit the great natural geographic variability of photoperiodic timing in P. apterus to explore its genetic basis. Genetic variants correlating with phenotypic differences will be causally tested by genome editing within the original genetic backgrounds. Both the established and the innovative strategies provide a complementary approach to the first molecular characterization of the seasonal photoperiodic timer in insects. The proposed research aspires to explain mechanisms underlying the critical physiological adaptation to changing seasons. Deciphering mechanisms underpinning widespread adaptation might bring general implications for environment-friendly pest control.
Summary
Daylength measuring devices such as the photoperiodic timer enable animals to anticipate and thus survive adverse seasons. This ability has contributed to the great success of insects living in temperate regions. Yet the basis of photoperiodic sensing remains elusive, because of the lack of suitable genetic models expressing photoperiod-dependent seasonal phenotypes. We have developed the linden bug, Pyrrhocoris apterus, into a genetically tractable model with a robust, photoperiod-dependent reproductive arrest (diapause). With the available tools, this insect has become ideal for deciphering the regulation of seasonality. The project has 3 clear and ambitious objectives: 1). Our goal is to define the molecular and anatomical bases of the photoperiodic timer. To achieve this, we propose to identify photoperiodic timer genes, genes regulating input to the timer, and early output markers, through an RNA interference screen(s). To define the molecular mechanism of the timer, we will employ genome editing to precisely alter properties of the key players. 2). Next, we will combine techniques of neuronal backfilling, in-vivo fluorescent reporters, and microsurgery to define the photoperiodic timer anatomically and to examine its spatial relationship to the circadian clock in the insect brain. 3). We will exploit the great natural geographic variability of photoperiodic timing in P. apterus to explore its genetic basis. Genetic variants correlating with phenotypic differences will be causally tested by genome editing within the original genetic backgrounds. Both the established and the innovative strategies provide a complementary approach to the first molecular characterization of the seasonal photoperiodic timer in insects. The proposed research aspires to explain mechanisms underlying the critical physiological adaptation to changing seasons. Deciphering mechanisms underpinning widespread adaptation might bring general implications for environment-friendly pest control.
Max ERC Funding
2 000 000 €
Duration
Start date: 2017-04-01, End date: 2022-03-31
Project acronym STEMpop
Project Mechanisms of stem cell population dynamics and reprogramming
Researcher (PI) Sara WICKSTRÖM
Host Institution (HI) HELSINGIN YLIOPISTO
Call Details Consolidator Grant (CoG), LS3, ERC-2017-COG
Summary How complex but stereotyped tissues are formed, maintained and regenerated through local growth, differentiation and remodeling is a fundamental open question in biology. Understanding how single cell behaviors are coordinated on the population level and how population-level dynamics is coupled to tissue architecture is required to resolve this question as well as to develop stem cell (SC) therapies and effective treatments against cancers.
As a self-renewing organ maintained by multiple distinct SC populations, the epidermis represents an outstanding, clinically highly relevant research paradigm to address this question. A key epidermal SC population are the hair follicle stem cells (HFSCs) that fuel hair follicle regeneration, repair epidermal injuries and, when deregulated, initiate carcinogenesis. The major obstacle in mechanistic understanding of HFSC regulation has been the lack of an in vitro culture system enabling their precise monitoring and manipulation. We have overcome this barrier by developing a method for long-term maintenance of multipotent HFSCs that recapitulates the complexity of HFSC fate decisions and dynamic crosstalk between HFSCs and their progeny.
This breakthrough invention puts me in the unique position to investigate how HFSCs self-organize into a network of SCs and progenitors through population-level signaling crosstalk and phenotypic plasticity. This project will uncover the spatiotemporal dynamics of HFSCs fate decisions and establish the role of the niche in this process (Aim1), decipher key gene-regulatory networks and epigenetic barriers that control phenotypic plasticity (Aim2), and discover druggable signaling networks that drive bi-directional reprogramming of HFSCs and their progeny (Aim3). By deconstructing complex tissue-level behaviors at an unprecedented spatiotemporal resolution this study has the potential to transform the fundaments of adult SC biology with immediate implications to regenerative medicine.
Summary
How complex but stereotyped tissues are formed, maintained and regenerated through local growth, differentiation and remodeling is a fundamental open question in biology. Understanding how single cell behaviors are coordinated on the population level and how population-level dynamics is coupled to tissue architecture is required to resolve this question as well as to develop stem cell (SC) therapies and effective treatments against cancers.
As a self-renewing organ maintained by multiple distinct SC populations, the epidermis represents an outstanding, clinically highly relevant research paradigm to address this question. A key epidermal SC population are the hair follicle stem cells (HFSCs) that fuel hair follicle regeneration, repair epidermal injuries and, when deregulated, initiate carcinogenesis. The major obstacle in mechanistic understanding of HFSC regulation has been the lack of an in vitro culture system enabling their precise monitoring and manipulation. We have overcome this barrier by developing a method for long-term maintenance of multipotent HFSCs that recapitulates the complexity of HFSC fate decisions and dynamic crosstalk between HFSCs and their progeny.
This breakthrough invention puts me in the unique position to investigate how HFSCs self-organize into a network of SCs and progenitors through population-level signaling crosstalk and phenotypic plasticity. This project will uncover the spatiotemporal dynamics of HFSCs fate decisions and establish the role of the niche in this process (Aim1), decipher key gene-regulatory networks and epigenetic barriers that control phenotypic plasticity (Aim2), and discover druggable signaling networks that drive bi-directional reprogramming of HFSCs and their progeny (Aim3). By deconstructing complex tissue-level behaviors at an unprecedented spatiotemporal resolution this study has the potential to transform the fundaments of adult SC biology with immediate implications to regenerative medicine.
Max ERC Funding
1 999 918 €
Duration
Start date: 2018-05-01, End date: 2023-04-30
