The programme

The Horizon Europe MSCA-Doctoral Network ETERNITY (“FuEl ThE bRaiN In healtThY aging and age-related diseases”) is a Consortium consisting of laboratories from Universities, Research Institutions and small-medium enterprises. ETERNITY offers a groundbreaking PhD level training in brain metabolism, focusing on metabolic and aged-related disorders.

 

Given the complementary expertise, ETERNITY will have excellent opportunities to delineate different molecular pathways underlying impaired brain metabolism as well as to identify novel pharmaceutical targets and/or nutritional interventional strategies that may ameliorate ageing and related disorders.

 

The 10 doctoral candidates (DCs) will have the unique opportunity to be trained by a transnational consortium with multidisciplinary expertise. Apart from the innovative and collaborative approach of the research programme, the DCs will also be exposed to a well-structured training programme in which cutting-edge methodology, innovation and transferable skills are key components.

The 10 Doctoral Candidates (DCs) will be part of an international, interdisciplinary and intersectoral network that includes expert in the field of metabolism and neurodegenerative disorders, bioinformatic systems biology methods, and cell-based therapies.


The main objectives of ETERNITY are the following:

1

To dissect the major pathways that control energy metabolism in different brain cells in physiology, during aging, and in response to specific diets

2

To determine specific metabolic pathways altered in Alzheimer’s Disease

3

To design and test interventional strategies for altered brain metabolism in age-related disorders

The consortium

The following organizations will directly recruit the DCs:

  • Università degli Studi di Milano (UMIL), Department of Pharmacological and Biomolecular Sciences, Milan, Italy
  • Neurocentre Magendie (INSERM), Bordeaux, France
  • Deutsches Zentrum fur Neurodegenerative Erkrankungen e.V. (DZNE), Bonn, Germany
  • Universidad de Salamanca (USAL), Institute of Functional Biology and Genomics, Salamanca, Spain
  • AvenCell Europe GmbH (AVENCELL), Dresden, Germany

Associated partners

The following Institutions and companies are part of the consortium and will contribute to training activities, including secondments:

  • European Brain Council (EBC), Brussels, Belgium
  • Charité Universitätsmedizin Berlin SPARK-BIH, Berlin, Germany
  • CF-Consulting s.r.l., Milan, Italy
  • Sofinol S.A., Lugano, Switzerland
  • EMBO Solutions GmbH, Heidelberg, Germany
  • The Visual Agency s.r.l., Milan, Italy

Individual Research Projects (DCs)

1

UMIL

RNF10 signaling pathway in physiology and Alzheimer Disease-induced mitochondrial dysfunction

DC1 will investigate the metabolic and gene expression profile of RNF10-silenced hippocampal neuronal cells of Alzheimer Disease mice to determine which metabolic programs and genes pathways are affected by RNF10. According, DC1 will assess the effect of specific dietary interventions on RNF10 pathway to restore Alzheimer Disease -associated alterations.

2

Identification of memory tasks-activated metabolic pathways in wild-type and Alzheimer disease​

UMIL

DC2 will investigate the dynamic distribution of metabolic substrates using liquid chromatography coupled to tandem mass spectrometry during episodic-like memory acquisition and retention. DC2 will also assess the effect of specific dietary interventions on the affected metabolic pathways and related memory functioning.

3

UMIL

Investigating the neuronal function of the novel regulator of mitochondria Zinc Finger CCCH-Type Containing 10 (Zc3h10)​

DC3 will evaluate the role in vitro and in vivo of Zc3h10 specifically in neurons, define its regulated metabolic pathways and the effects of the lack of Zc3h10 in neuron on the metabolism of the other brain cells. Moreover, DC3 will also validate the Zc3h10 regulated pathways in induced pluripotent stem cells-derived neurons and test novel chemicals to restore and or improve mitochondrial function.

4

Role of bioenergetic pathways in the microglial inflammatory response to an obesogenic diet​

INSERM

DC4 will use a preclinical model of obesity, with the main goals to decipher the fine bioenergetic alterations induced in hypothalamic microglia under obesity, in relation with their functional and proliferation status; and to understand how these microglial changes affect hypothalamic neural networks.

5

INSERM

Role of mTOR pathway in the metabolic response of microglia in a mouse model of obesity​​

DC5 will unravel the role of microglial mammalian target of rapamycin (mTOR) activation in obesity-associated neuronal alterations. DC5 will evaluate if the consumption of an obesogenic diet reprograms microglial bioenergetics in a mTOR -dependent manner in preclinical animal model of obesity.

6

Mitochondrial bioenergetics in microglia differentiation and upon metabolic insults during aging​

DZNE

DC6 will investigate the impact of mitochondrial function/dysfunction in microglia development and activity upon dietary challenges in induced pluripotent stem cells-derived microglia and in mouse models of mitochondrial diseases. DC6 will use a multi-omics approach, with a special focus on potential pathways that may take part in compensatory mechanisms and enable the survival of cells exposed to metabolic challenges.

7

DZNE

How brain mitochondria bioenergetics affect the inflammatory phenotype of aged microglia​

DC7 will assess mitochondrial fitness, mammalian target of rapamycin (mTOR) and insulin signaling in brain cells isolated from young and aged mice, as well as in induced pluripotent stem cells-derived neuron and microglia. Furthermore, in co-culture experiments, DC7 will assess the possibility that mitochondrial defects in one cell type, i.e. neurons, affect mTOR signaling in microglia, increasing their inflammatory phenotype. Finally, DC7 will also investigate in vivo the effect of specific dietary interventions or decreased mTOR signaling specifically in microglia in young and aged mice to counteract their pro-inflammatory phenotype and assess the effect on cognitive function.

8

Isocaloric twice-a-day diet and brain mitochondria during aging.​

USAL

DC8 will develop an activity plan aimed to ascertain whether feeding mice with isocaloric twice-a-day diet (ITAD) improves the mitochondrial efficiency and autophagic machinery of neurons and astrocytes in the aged mice. Mice will be fed with either a standard, high-fat diet (HFD), or HFD- ITAD diets for up the age of 18 months.

9

USAL

Isocaloric twice-a-day diet in learning and memory during aging.​​

DC9 will develop an activity plan aimed to ascertain whether feeding mice with Isocaloric twice-a-day diet (ITAD) improves the immunohistochemical signature of the hippocampus and learning in the aged mice. Mice will be fed with either a standard, high-fat diet (HFD), or HFD- ITAD diets for up the age of 18 months.

10

Chimeric antigen receptor T (CAR-T) cells to target aging, neurodegeneration and senescence.​

AVENCELL

DC10’s work will be focused on the development and validation of a chimeric antigen receptor T (CAR-T)-cell-based approach to tackle cellular senescence, aging and age-associated pathology. Based on surface markers selectively expressed on senescent cells, DC10 will develop CARs to retarget T cells to senescent cells. DC10 will then perform proof-of-concept studies to examine whether these CAR-T-cells eliminate senescent cells in vitro and in vivo. DC10 will also assess in mouse models if CAR-T-cell-based treatment alleviates neurodegeneration as well as cognitive dysfunction associated with aging and metabolic insults.

Work packages (WP)

To achieve ETERNITY objectives, the following work packages (WPs) will be implemented:

1

Elucidation of brain metabolism alterations during ageing and under various dietary conditions

Start month

M6

End month

M42

Activity type

Research

Lead beneficiary

INSERM
DZNE

Researcher
involvment

DC1
DC2
DC3
DC4
DC5
DC6
DC7
DC8
DC9
DC10

2

Identification of profile changes in brain metabolism in AD

Start month

M6

End month

M42

Activity type

Research

Lead beneficiary

INSERM
DZNE

Researcher
involvment

DC1
DC2
DC3
DC4
DC5
DC6
DC7
DC8
DC9
DC10

3

Validation of metabolic targets and proof of concepts towards translation approach

Start month

M6

End month

M42

Activity type

Research

Lead beneficiary

USAL
GEMoaB

Researcher
involvment

DC1
DC2
DC3
DC4
DC5
DC6
DC7
DC8
DC9
DC10

4

Training
activities

Start month

M6

End month

M42

Activity type

Training

Lead beneficiary

UMIL

Researcher
involvment

DC1
DC2
DC3
DC4
DC5
DC6
DC7
DC8
DC9
DC10

5

Project
management

Start month

M1

End month

M48

Activity type

Management

Lead beneficiary

UMIL

Researcher
involvment

DC1
DC2
DC3
DC4
DC5
DC6
DC7
DC8
DC9
DC10

6

Dissemination, communication and exploitation

Start month

M1

End month

M48

Activity type

Management

Lead beneficiary

UMIL

Researcher
involvment

DC1
DC2
DC3
DC4
DC5
DC6
DC7
DC8
DC9
DC10

Eligibility requirements

There are strict eligibility requirements for the ESR positions.
Please ensure to be qualified before applying, as ineligible candidates cannot be considered. The Recruitment board will pay special attention to respect gender balance.

Questions and contacts

For further information please contact us

eternity@unimi.it

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