Project acronym DENDROWORLD
Project Mucosal dendritic cells in intestinal homeostasis and bacteria-related diseases
Researcher (PI) Maria Rescigno
Host Institution (HI) ISTITUTO EUROPEO DI ONCOLOGIA SRL
Call Details Starting Grant (StG), LS3, ERC-2007-StG
Summary The bacterial microflora has always been regarded as beneficial for the host but recent studies have shown that this symbiosis has risks as well as benefits. Although active mechanisms allow tolerating the commensal flora, the physiological stress that is associated with the symbionts’ metabolism can exhaust the intestinal barrier resulting in serious effects on the health of the host. Protracted immune deregulations can lead to severe disorders including diabetes, cancer and inflammatory bowel disease (IBD). Several mechanisms and players are involved in the maintenance of intestinal immune homeostasis, including T regulatory cells and Immunoglobulin (Ig)-A. In this proposal we focus our attention on dendritic cells (DCs) for their ability to induce both tolerance and immunity by regulating B and T cell responses. We have recently shown that DC function is controlled by intestinal epithelial cell (EC) derived factors and in particular by Thymic stromal lymphopoietin (TSLP). EC-conditioned DCs acquire a ‘mucosal’ phenotype as they are prone to activate T regulatory cells and IgA responses. Three major issues related to the maintenance and disruption of intestinal immune homeostasis will be explored in this project: 1) What are the mediators and mechanisms that regulate the interaction between intestinal epithelial cells and dendritic cells? What is the function of TSLP? 2) Which are the sites and players for the activation of an IgA response to pathogenic and commensal bacteria? Can we visualize them in vivo? 3) Can prolonged infections or bacterial products promote intestinal tumour development? Are there different bacterial constituents acting as inducers or protectors of carcinogenesis? What is the role of Toll-like receptors?
Summary
The bacterial microflora has always been regarded as beneficial for the host but recent studies have shown that this symbiosis has risks as well as benefits. Although active mechanisms allow tolerating the commensal flora, the physiological stress that is associated with the symbionts’ metabolism can exhaust the intestinal barrier resulting in serious effects on the health of the host. Protracted immune deregulations can lead to severe disorders including diabetes, cancer and inflammatory bowel disease (IBD). Several mechanisms and players are involved in the maintenance of intestinal immune homeostasis, including T regulatory cells and Immunoglobulin (Ig)-A. In this proposal we focus our attention on dendritic cells (DCs) for their ability to induce both tolerance and immunity by regulating B and T cell responses. We have recently shown that DC function is controlled by intestinal epithelial cell (EC) derived factors and in particular by Thymic stromal lymphopoietin (TSLP). EC-conditioned DCs acquire a ‘mucosal’ phenotype as they are prone to activate T regulatory cells and IgA responses. Three major issues related to the maintenance and disruption of intestinal immune homeostasis will be explored in this project: 1) What are the mediators and mechanisms that regulate the interaction between intestinal epithelial cells and dendritic cells? What is the function of TSLP? 2) Which are the sites and players for the activation of an IgA response to pathogenic and commensal bacteria? Can we visualize them in vivo? 3) Can prolonged infections or bacterial products promote intestinal tumour development? Are there different bacterial constituents acting as inducers or protectors of carcinogenesis? What is the role of Toll-like receptors?
Max ERC Funding
1 195 680 €
Duration
Start date: 2008-07-01, End date: 2013-06-30
Project acronym DissectPcG
Project Dissecting the Function of Multiple Polycomb Group Complexes in Establishing Transcriptional Identity
Researcher (PI) Diego PASINI
Host Institution (HI) UNIVERSITA DEGLI STUDI DI MILANO
Call Details Consolidator Grant (CoG), LS3, ERC-2016-COG
Summary The activities of the Polycomb group (PcG) of repressive chromatin modifiers are required to maintain correct transcriptional identity during development and differentiation. These activities are altered in a variety of tumours by gain- or loss-of-function mutations, whose mechanistic aspects still remain unclear.
PcGs can be classified in two major repressive complexes (PRC1 and PRC2) with common pathways but distinct biochemical activities. PRC1 catalyses histone H2A ubiquitination of lysine 119, and PRC2 tri-methylation of histone H3 lysine 27. However, PRC1 has a more heterogeneous composition than PRC2, with six mutually exclusive PCGF subunits (PCGF1–6) essential for assembling distinct PRC1 complexes that differ in subunit composition but share the same catalytic core.
While up to six different PRC1 forms can co-exist in a given cell, the molecular mechanisms regulating their activities and their relative contributions to general PRC1 function in any tissue/cell type remain largely unknown. In line with this biochemical heterogeneity, PRC1 retains broader biological functions than PRC2. Critically, however, no molecular analysis has yet been published that dissects the contribution of each PRC1 complex in regulating transcriptional identity.
We will take advantage of newly developed reagents and unpublished genetic models to target each of the six Pcgf genes in either embryonic stem cells or mouse adult tissues. This will systematically dissect the contributions of the different PRC1 complexes to chromatin profiles, gene expression programs, and cellular phenotypes during stem cell self-renewal, differentiation and adult tissue homeostasis. Overall, this will elucidate some of the fundamental mechanisms underlying the establishment and maintenance of cellular identity and will allow us to further determine the molecular links between PcG deregulation and cancer development in a tissue- and/or cell type–specific manner.
Summary
The activities of the Polycomb group (PcG) of repressive chromatin modifiers are required to maintain correct transcriptional identity during development and differentiation. These activities are altered in a variety of tumours by gain- or loss-of-function mutations, whose mechanistic aspects still remain unclear.
PcGs can be classified in two major repressive complexes (PRC1 and PRC2) with common pathways but distinct biochemical activities. PRC1 catalyses histone H2A ubiquitination of lysine 119, and PRC2 tri-methylation of histone H3 lysine 27. However, PRC1 has a more heterogeneous composition than PRC2, with six mutually exclusive PCGF subunits (PCGF1–6) essential for assembling distinct PRC1 complexes that differ in subunit composition but share the same catalytic core.
While up to six different PRC1 forms can co-exist in a given cell, the molecular mechanisms regulating their activities and their relative contributions to general PRC1 function in any tissue/cell type remain largely unknown. In line with this biochemical heterogeneity, PRC1 retains broader biological functions than PRC2. Critically, however, no molecular analysis has yet been published that dissects the contribution of each PRC1 complex in regulating transcriptional identity.
We will take advantage of newly developed reagents and unpublished genetic models to target each of the six Pcgf genes in either embryonic stem cells or mouse adult tissues. This will systematically dissect the contributions of the different PRC1 complexes to chromatin profiles, gene expression programs, and cellular phenotypes during stem cell self-renewal, differentiation and adult tissue homeostasis. Overall, this will elucidate some of the fundamental mechanisms underlying the establishment and maintenance of cellular identity and will allow us to further determine the molecular links between PcG deregulation and cancer development in a tissue- and/or cell type–specific manner.
Max ERC Funding
2 000 000 €
Duration
Start date: 2017-11-01, End date: 2022-10-31
Project acronym ERMITO
Project Molecular Anatomy and Pathophysiology of the endoplasmic reticulum-mitochondria interface
Researcher (PI) Luca Scorrano
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PADOVA
Call Details Starting Grant (StG), LS3, ERC-2011-StG_20101109
Summary Organelles are not randomly organized in the cytoplasm of the cell, but often are orderly arranged in mutual relationships that depend on physical, protein bounds. Understanding the molecular nature of the tethers that regulate relative position and juxtaposition of the organelles is one of the main quests of cell biology, given their functional importance. For example, the juxtaposition between mitochondria and endoplasmic reticulum (ER) has been suggested by us and others to crucially impact on Ca2+ signalling and apoptosis. We recently identified the first structural ER-mitochondrial tether in mitofusin 2 (Mfn2), a pro-fusion mitochondria-shaping protein. A fraction of Mfn2 is also located on the ER regulating its morphology, and acting in trans to tether it to mitochondria. The tethering function of Mfn2 impacts on the transmission of Ca2+ signals between the two organelles and is regulated by the oncosuppressor trichoplein/mitostatin. Mfn2 is likely only one of the tethers, as others exist in yeast. Furthermore, the dynamicity of the ER-mitochondria contact is known, but remains poorly understood. Therefore, a clear picture of the anatomy and pathophsyiology of ER-mitochondrial connection is far from being reached.
Here we hypothesize that ER-mitochondrial contacts are crucial specialized hubs of cellular signalling whose architecture is modulated by cellular cues, impacting on integrated signalling cascades and ultimately affecting cellular function. To address this hypothesis we wish to setup a research project that aims at (i) increasing our knowledge on the molecular nature of tethers and modulators of ER-mitochondrial tethers in mammalian cells; (ii) clarifying how mitochondrial and ER function are controlled by the tethering; (iii) addressing how juxtaposition influences complex cellular responses including autophagy and cell death; (iv) elucidating the role of tethering in vivo by generating animal models with defined ER-mitochondrial distance.
Summary
Organelles are not randomly organized in the cytoplasm of the cell, but often are orderly arranged in mutual relationships that depend on physical, protein bounds. Understanding the molecular nature of the tethers that regulate relative position and juxtaposition of the organelles is one of the main quests of cell biology, given their functional importance. For example, the juxtaposition between mitochondria and endoplasmic reticulum (ER) has been suggested by us and others to crucially impact on Ca2+ signalling and apoptosis. We recently identified the first structural ER-mitochondrial tether in mitofusin 2 (Mfn2), a pro-fusion mitochondria-shaping protein. A fraction of Mfn2 is also located on the ER regulating its morphology, and acting in trans to tether it to mitochondria. The tethering function of Mfn2 impacts on the transmission of Ca2+ signals between the two organelles and is regulated by the oncosuppressor trichoplein/mitostatin. Mfn2 is likely only one of the tethers, as others exist in yeast. Furthermore, the dynamicity of the ER-mitochondria contact is known, but remains poorly understood. Therefore, a clear picture of the anatomy and pathophsyiology of ER-mitochondrial connection is far from being reached.
Here we hypothesize that ER-mitochondrial contacts are crucial specialized hubs of cellular signalling whose architecture is modulated by cellular cues, impacting on integrated signalling cascades and ultimately affecting cellular function. To address this hypothesis we wish to setup a research project that aims at (i) increasing our knowledge on the molecular nature of tethers and modulators of ER-mitochondrial tethers in mammalian cells; (ii) clarifying how mitochondrial and ER function are controlled by the tethering; (iii) addressing how juxtaposition influences complex cellular responses including autophagy and cell death; (iv) elucidating the role of tethering in vivo by generating animal models with defined ER-mitochondrial distance.
Max ERC Funding
1 499 995 €
Duration
Start date: 2012-01-01, End date: 2016-12-31
Project acronym LEPTINMS
Project Leptin, metabolic state and natural regulatory T cells: cellular and molecular basis for a novel immune intervention in autoimmunity
Researcher (PI) Giuseppe Matarese
Host Institution (HI) CONSIGLIO NAZIONALE DELLE RICERCHE
Call Details Starting Grant (StG), LS3, ERC-2007-StG
Summary Our Group has been investigating the cellular and molecular mechanisms involving leptin, the adipocyte-derived hormone, in the pathogenesis of autoimmunity such as experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS).We analyzed the serum and cerebro-spinal fluid (CSF) leptin secretion and the interaction between serum leptin and naturally occurring Foxp3+CD4+CD25+ regulatory T cells (Tregs) in naïve-to-therapy multiple sclerosis (MS) patients. Leptin production was significantly increased in serum and CSF of MS patients and correlated with interferon-gamma (IFN-g) secretion in the CSF.T cell lines against human myelin basic protein (hMBP) produced leptin and upregulated the expression of the leptin receptor (ObR) after activation with hMBP; treatment with either anti-leptin or anti-leptin receptor neutralizing antibodies inhibited in vitro proliferation to hMBP.Interestingly, in the MS patients an inverse correlation between serum leptin and percentage of circulating Tregs was also observed. Moreover, treatment of EAE-susceptible mice with a leptin antagonist increased the percentage of Tregs and ameliorated disease clinical course and progression in proteolipid protein peptide (PLP139-151)-induced EAE.These findings show for the first time an inverse relationship between leptin secretion and the frequency of Tregs in EAE and MS.In the present project, we intend to analyze in vitro and in vivo, the relationship between leptin and Tregs in human and in animal models, studying at molecular and cellular level the effect of leptin and its neutralization on the survival, proliferation and cytokine secretion of Tregs.Despite recent advances, the precise requirements for the physiological development of Tregs such as the necessary milieu and their molecular/biochemical requirements, remain enigmatic.Understanding these events will be important for the generation of Tregs which could have potential implications for treatment of autoimmunity.
Summary
Our Group has been investigating the cellular and molecular mechanisms involving leptin, the adipocyte-derived hormone, in the pathogenesis of autoimmunity such as experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS).We analyzed the serum and cerebro-spinal fluid (CSF) leptin secretion and the interaction between serum leptin and naturally occurring Foxp3+CD4+CD25+ regulatory T cells (Tregs) in naïve-to-therapy multiple sclerosis (MS) patients. Leptin production was significantly increased in serum and CSF of MS patients and correlated with interferon-gamma (IFN-g) secretion in the CSF.T cell lines against human myelin basic protein (hMBP) produced leptin and upregulated the expression of the leptin receptor (ObR) after activation with hMBP; treatment with either anti-leptin or anti-leptin receptor neutralizing antibodies inhibited in vitro proliferation to hMBP.Interestingly, in the MS patients an inverse correlation between serum leptin and percentage of circulating Tregs was also observed. Moreover, treatment of EAE-susceptible mice with a leptin antagonist increased the percentage of Tregs and ameliorated disease clinical course and progression in proteolipid protein peptide (PLP139-151)-induced EAE.These findings show for the first time an inverse relationship between leptin secretion and the frequency of Tregs in EAE and MS.In the present project, we intend to analyze in vitro and in vivo, the relationship between leptin and Tregs in human and in animal models, studying at molecular and cellular level the effect of leptin and its neutralization on the survival, proliferation and cytokine secretion of Tregs.Despite recent advances, the precise requirements for the physiological development of Tregs such as the necessary milieu and their molecular/biochemical requirements, remain enigmatic.Understanding these events will be important for the generation of Tregs which could have potential implications for treatment of autoimmunity.
Max ERC Funding
880 000 €
Duration
Start date: 2008-07-01, End date: 2011-10-31
Project acronym MAMMASTEM
Project Molecular mechanisms of the regulation of mammary stem cell homeostasis and their subversion in cancer
Researcher (PI) Pier Paolo Di Fiore
Host Institution (HI) IFOM FONDAZIONE ISTITUTO FIRC DI ONCOLOGIA MOLECOLARE
Call Details Advanced Grant (AdG), LS3, ERC-2008-AdG
Summary Stem cells (SCs) are thought to be integral to the development and progression of cancer, and their eradication may be essential for the cure of cancer. Yet, direct proof is lacking due to our poor understanding of the molecular differences between normal and cancer SCs. We will investigate normal and cancer mammary stem cells (MSCs) by focusing on the role of the cell fate determinant Numb in two signaling axes: Numb:Notch and Numb:p53. Numb is a tumor suppressor in human breast cancer. Its expression is lost, through increased degradation, in ~50% of breast cancers. These Numbneg cancers display overall poorer prognosis. Mechanistically, loss of Numb causes increased Notch signaling and decreased p53 signaling. Thus, Numb controls both an oncogenic pathway (the Numb:Notch axis) and a tumor suppressor one (the Numb:p53 axis). We showed that Numb is asymmetrically partitioned at the first division of normal MSCs and hypothesize that loss of Numb affects the kinetics of division and MSC fate. Our specific aims are to: 1. Define the role of the Numb:Notch and Numb:p53 axes in normal and cancer MSCs. We will exploit our capacity to propagate and isolate MSCs to near-purity, for biological, biochemical and omics approaches. In this task, we will integrate knowledge derived from the analysis of real human cancers and of genetically-defined mouse models. 2. Define the broader biological context of Numb impact in stem cell biology, by analyzing the role of endocytosis in MSC fate determination. This is justified by the fact that Numb is an endocytic protein and that data in Drosophila indicate a complex role of endocytosis in cell fate specification. 3. Identify the E3 ligase responsible for Numb degradation in Numbneg breast tumors, in order to obtain druggable targets to restore Numb levels in these tumors. If successful, our work will elucidate major mechanisms of normal and cancer stem cell regulation, and provide tools for SC-specific therapeutic intervention.
Summary
Stem cells (SCs) are thought to be integral to the development and progression of cancer, and their eradication may be essential for the cure of cancer. Yet, direct proof is lacking due to our poor understanding of the molecular differences between normal and cancer SCs. We will investigate normal and cancer mammary stem cells (MSCs) by focusing on the role of the cell fate determinant Numb in two signaling axes: Numb:Notch and Numb:p53. Numb is a tumor suppressor in human breast cancer. Its expression is lost, through increased degradation, in ~50% of breast cancers. These Numbneg cancers display overall poorer prognosis. Mechanistically, loss of Numb causes increased Notch signaling and decreased p53 signaling. Thus, Numb controls both an oncogenic pathway (the Numb:Notch axis) and a tumor suppressor one (the Numb:p53 axis). We showed that Numb is asymmetrically partitioned at the first division of normal MSCs and hypothesize that loss of Numb affects the kinetics of division and MSC fate. Our specific aims are to: 1. Define the role of the Numb:Notch and Numb:p53 axes in normal and cancer MSCs. We will exploit our capacity to propagate and isolate MSCs to near-purity, for biological, biochemical and omics approaches. In this task, we will integrate knowledge derived from the analysis of real human cancers and of genetically-defined mouse models. 2. Define the broader biological context of Numb impact in stem cell biology, by analyzing the role of endocytosis in MSC fate determination. This is justified by the fact that Numb is an endocytic protein and that data in Drosophila indicate a complex role of endocytosis in cell fate specification. 3. Identify the E3 ligase responsible for Numb degradation in Numbneg breast tumors, in order to obtain druggable targets to restore Numb levels in these tumors. If successful, our work will elucidate major mechanisms of normal and cancer stem cell regulation, and provide tools for SC-specific therapeutic intervention.
Max ERC Funding
2 274 862 €
Duration
Start date: 2009-03-01, End date: 2014-02-28
Project acronym MetEpiStem
Project Dissecting the crosstalk between metabolism and transcriptional regulation in pluripotent stem cells.
Researcher (PI) Graziano MARTELLO
Host Institution (HI) UNIVERSITA DEGLI STUDI DI PADOVA
Call Details Starting Grant (StG), LS3, ERC-2016-STG
Summary Pluripotent Stem cells (PSCs) can give rise to all differentiated cells of the body and the germ line, which makes them conceptually fascinating and a valuable tool for regenerative medicine. Mouse PSCs are devoid of any developmental restriction partly thanks to their “open” chromatin, characterised by remarkably low levels of repressive epigenetic modifications. Metabolism is a key feature that can be adjusted to meet the cell’s needs, and that has the potential to feedback on transcription and epigenetics. How metabolism is regulated in PSCs and whether this is important for their biology remains largely unknown.
We recently found a new molecular mechanism by which energy production is coupled to pluripotency. Here we propose to deepen our understanding of how metabolism, epigenetics and transcription are reciprocally regulated for the self-renewal and differentiation of PSCs. To gain insights into how metabolism is dynamically regulated in concert with the transcriptome and epigenome, we will also use somatic cell reprogramming into PSCs, a process in which both the metabolic and epigenetic profiles must be reset to match those of PSCs. Moreover, taking advantage of the recent generation of novel human PSCs sharing most of the transcriptional and epigenetic features found in naïve mouse PSCs, we will explore how metabolic regulatory mechanisms key for the generation and maintenance of pluripotency are conserved throughout evolution. Altogether, large-scale transcriptional, epigenetic and metabolic profiling of PSCs, combined with cutting edge technologies for their generation, expansion and genetic manipulation, will give us the unprecedented opportunity to build a comprehensive computational model of the metabolic network in PSCs, and to study how gene transcription and metabolism regulate each other.
Summary
Pluripotent Stem cells (PSCs) can give rise to all differentiated cells of the body and the germ line, which makes them conceptually fascinating and a valuable tool for regenerative medicine. Mouse PSCs are devoid of any developmental restriction partly thanks to their “open” chromatin, characterised by remarkably low levels of repressive epigenetic modifications. Metabolism is a key feature that can be adjusted to meet the cell’s needs, and that has the potential to feedback on transcription and epigenetics. How metabolism is regulated in PSCs and whether this is important for their biology remains largely unknown.
We recently found a new molecular mechanism by which energy production is coupled to pluripotency. Here we propose to deepen our understanding of how metabolism, epigenetics and transcription are reciprocally regulated for the self-renewal and differentiation of PSCs. To gain insights into how metabolism is dynamically regulated in concert with the transcriptome and epigenome, we will also use somatic cell reprogramming into PSCs, a process in which both the metabolic and epigenetic profiles must be reset to match those of PSCs. Moreover, taking advantage of the recent generation of novel human PSCs sharing most of the transcriptional and epigenetic features found in naïve mouse PSCs, we will explore how metabolic regulatory mechanisms key for the generation and maintenance of pluripotency are conserved throughout evolution. Altogether, large-scale transcriptional, epigenetic and metabolic profiling of PSCs, combined with cutting edge technologies for their generation, expansion and genetic manipulation, will give us the unprecedented opportunity to build a comprehensive computational model of the metabolic network in PSCs, and to study how gene transcription and metabolism regulate each other.
Max ERC Funding
1 498 232 €
Duration
Start date: 2017-10-01, End date: 2022-09-30
Project acronym ROMA
Project To the root of organ growth: the control of root meristem activity in Arabidopsis
Researcher (PI) Sabrina Sabatini
Host Institution (HI) UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA
Call Details Starting Grant (StG), LS3, ERC-2010-StG_20091118
Summary In animals, the formation and growth of new organs cease at the completion of development; in plants, the body is continuously built throughout the plant lifespan. In addition, in plants there is virtually no cell migration due to rigid cell walls: this provides a unique opportunity for dissecting the relations between pattern formation and final organ structure.
Plant post-embryonic development takes place in localized regions called meristems. In the root of Arabidopsis thaliana, stem cells in the apical region of the meristem self-renew and produce daughter cells that differentiate in the distal meristem transition zone. To ensure root growth, the rate of cell differentiation must equal the rate of generation of new cells. Recent work of the proponent has shown that maintenance of the Arabidopsis root meristem size - and consequently root growth - is controlled by the interaction between two hormones in the meristem transition zone: cytokinin, which promotes cell differentiation, and auxin, which promotes cell division, and has unveiled the regulatory circuit underlying this interaction.
Scope of this proposal is to clarify how the cytokinin/auxin interaction influences the activities of the entire root meristem, thus ensuring a balance between cell differentiation and cell division.
In particular, the work proposed aims to:
- Clarify how the cytokinin/auxin interaction is perceived in the transition zone to bring about synchronous differentiation of all cell files of the distal meristem.
- Understand how the cytokinin/auxin interaction maintains a balance between cell differentiation in the (distal) transition zone and cell division in the (apical) stem cell niche.
- Unveil other inputs and regulatory circuits that interact with the cytokinin/auxin regulatory circuit in controlling root growth.
These goals will be achieved via the identification of genes involved in these processes. Hypothesis-driven experiments will allow verifying the role of candidate genes, and genetic and genome-wide approaches will allow identifying new genes.
In these activities, we will take advantage of state-of-the-art techniques, including tissue- and cell-specific gene expression techniques, analysis of microarrays from cell lines isolated via cell sorter, light microscopy and confocal imaging techniques, as well as classic genetic, physiological and pharmacological approaches.
The experimental results of these research lines will be integrated into computational models with the ultimate goal of describing the mechanisms of root growth and its control
Summary
In animals, the formation and growth of new organs cease at the completion of development; in plants, the body is continuously built throughout the plant lifespan. In addition, in plants there is virtually no cell migration due to rigid cell walls: this provides a unique opportunity for dissecting the relations between pattern formation and final organ structure.
Plant post-embryonic development takes place in localized regions called meristems. In the root of Arabidopsis thaliana, stem cells in the apical region of the meristem self-renew and produce daughter cells that differentiate in the distal meristem transition zone. To ensure root growth, the rate of cell differentiation must equal the rate of generation of new cells. Recent work of the proponent has shown that maintenance of the Arabidopsis root meristem size - and consequently root growth - is controlled by the interaction between two hormones in the meristem transition zone: cytokinin, which promotes cell differentiation, and auxin, which promotes cell division, and has unveiled the regulatory circuit underlying this interaction.
Scope of this proposal is to clarify how the cytokinin/auxin interaction influences the activities of the entire root meristem, thus ensuring a balance between cell differentiation and cell division.
In particular, the work proposed aims to:
- Clarify how the cytokinin/auxin interaction is perceived in the transition zone to bring about synchronous differentiation of all cell files of the distal meristem.
- Understand how the cytokinin/auxin interaction maintains a balance between cell differentiation in the (distal) transition zone and cell division in the (apical) stem cell niche.
- Unveil other inputs and regulatory circuits that interact with the cytokinin/auxin regulatory circuit in controlling root growth.
These goals will be achieved via the identification of genes involved in these processes. Hypothesis-driven experiments will allow verifying the role of candidate genes, and genetic and genome-wide approaches will allow identifying new genes.
In these activities, we will take advantage of state-of-the-art techniques, including tissue- and cell-specific gene expression techniques, analysis of microarrays from cell lines isolated via cell sorter, light microscopy and confocal imaging techniques, as well as classic genetic, physiological and pharmacological approaches.
The experimental results of these research lines will be integrated into computational models with the ultimate goal of describing the mechanisms of root growth and its control
Max ERC Funding
1 475 999 €
Duration
Start date: 2010-11-01, End date: 2016-10-31
