Job ID: 104550

10 PhD positions within the program Horizon Europe Marie Skłodowska-Curie Actions Doctoral Networks “ETERNITY” “FuEl ThE bRaiN In healtThY aging and age-related diseases”

Position: Ph.D. Student

Deadline: 15 April 2023

Contract Length: 3 years

City: Milan

Country: Italy

Institution: Università degli Studi di Milano

Department:

Description:

We are seeking 10 highly motivated fellows to pursue a career in science, obtain a PhD abroad, and work in one of the three-year research projects we are offering under the Marie Sklodowska-Curie Doctoral Network “ETERNITY – FuEl ThE bRaiN In healtThY aging and age-related diseases”. ETERNITY has the visionary aim to investigate how metabolic pathways are regulated in the brain in response to physio-pathological cues, with the final goal to provide proof of concept for innovative metabolic targets. The 10 PhD students 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 organizations that will recruit the 10 PhD students are:

Università degli Studi di Milano, Milan, Italy: 3 PhD positions

DZNE, Bonn, Germany: 2 PhD positions

Neurocentre Magendie (INSERM), Bordeaux, France: 2 PhD positions

Universidad de Salamanca, Salamanca, Spain: 2 PhD positions

AvenCell Europe GmbH Dresden, Germany: 1 PhD positions

The individual projects are described as follow:

Project 1: RNF10 signaling pathway in physiology and Alzheimer Disease-induced mitochondrial dysfunction. (Supervisors: Elena Marcello and Monica Di Luca, Università degli Studi di Milano, https://eng.disfeb.unimi.it/ecm/home).

PhD student1 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, PhD student1 will assess the effect of specific dietary interventions on RNF10 pathway to restore Alzheimer Disease -associated alterations

Project 2: Identification of memory tasks-activated metabolic pathways in wild-type and Alzheimer disease. (Supervisors: Diego Scheggia and Nico Mitro, Università degli Studi di Milano, https://eng.disfeb.unimi.it/ecm/home).

PhD student 2 will investigate the dynamic distribution of metabolic substrates using liquid chromatography coupled to tandem mass spectrometry during episodic-like memory acquisition and retention. PhD student 2 will also assess the effect of specific dietary interventions on the affected metabolic pathways and related memory functioning.

Project 3: Investigating the neuronal function of the novel regulator of mitochondria Zinc Finger CCCH-Type Containing 10 (Zc3h10) (Supervisors: Nico Mitro and Elena Marcello, Università degli Studi di Milano, https://eng.disfeb.unimi.it/ecm/home).

PhD student 3 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, PhD student 3 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.

Project 4: Role of bioenergetic pathways in the microglial inflammatory response to an obesogenic diet. (Supervisor: Agnès Nadjar, INSERM, https://www.bordeaux-neurocampus.fr/en/staff/agnes-nadjar/)

PhD student 4 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. 

Project 5: Role of mTOR pathway in the metabolic response of microglia in a mouse model of obesity. (Supervisor: Agnès Nadjar, INSERM, https://www.bordeaux-neurocampus.fr/en/staff/agnes-nadjar/)

PhD student 5 will unravel the role of microglial mammalian target of rapamycin (mTOR) activation in obesity-associated neuronal alterations. PhD student 5 will evaluate if the consumption of an obesogenic diet reprograms microglial bioenergetics in a mTOR -dependent manner in preclinical animal model of obesity.

Project 6: Mitochondrial bioenergetics in microglia differentiation and upon metabolic insults during aging. (Supervisor: Daniele Bano and Melania Capasso, DZNE https://www.dzne.de/en/research/research-areas/fundamental-research/research-groups/bano/research-areasfocus/).

PhD student 6 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. PhD student 6 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.

Project 7: How brain mitochondria bioenergetics affect the inflammatory phenotype of aged microglia. (Supervisor: Melania Capasso and Daniele Bano, DZNE https://www.dzne.de/en/research/research-areas/fundamental-research/research-groups/capasso/research-areasfocus/).

PhD student 7 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, PhD student 7 will assess the possibility that mitochondrial defects in one cell type, i.e. neurons, affect mTOR signaling in microglia, increasing their inflammatory phenotype. Finally, PhD student 7 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.

Project 8: Isocaloric twice-a-day diet and brain mitochondria during aging. (Supervisors: Juan Pedro Bolaños and Angeles Almeida, Universidad de Salamanca, https://ibfg.usal-csic.es/juan-pedro-bolanos-en.html)

PhD student 8 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.

Project 9: Isocaloric twice-a-day diet in learning and memory during aging. (Supervisors: Juan Pedro Bolaños and Angeles Almeida, Universidad de Salamanca, https://ibfg.usal-csic.es/juan-pedro-bolanos-en.html)

PhD student 9 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.

Project 10: Chimeric antigen receptor T (CAR-T) cells to target aging, neurodegeneration and senescence. (Supervisor: Armin Ehninger, AvenCell, https://avencell.com/).

PhD student 10’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, PhD student 10 will develop CARs to retarget T cells to senescent cells. PhD student 10 will then perform proof-of-concept studies to examine whether these CAR-T-cells eliminate senescent cells in vitro and in vivo. PhD student 10 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.

ELIGIBILITY REQUIREMENTS

There are strict eligibility requirements for the PhD positions enrolled trough the Marie Sklodowska-Curie Action-Doctoral Network:

  1. Applicants MUST NOT BE in possession of a PhD.
  2. Applicants MUST NOT HAVE resided or carried out their main activity (work, studies, etc.) in the country of the recruiting beneficiary for more than 12 months in the 36 months immediately before their recruitment date.

Further financial and eligibility rules are reported at the following link: https://ec.europa.eu/info/funding-tenders/opportunities/docs/2021-2027/horizon/wp-call/2021-2022/wp-2-msca-actions_horizon-2021-2022_en.pdf .

Additional eligibility criteria are required by the ETERNITY consortium:

  • Highly motivated and science-driven person holding a master’s degree or equivalent in Life Science or related disciplines. A background in metabolism and/or neuroscience or related areas of biology (e.g., neurobiology, molecular biology, (epi)-genetics) is an added value.
  • Applicant must hold an English language certificate (at least B2 level).

HOW TO APPLY

Applications must be submitted exclusively through the dedicated web site www.projecteternity.eu starting from February 20, 2023, and no later than April 15, 2023, 17:00 Central European Time (5 p.m.).

Each applicant can apply to individual projects within the group call, with a possibility to express interests in up to three projects, ranking them according to the preferences.

For further information please contact: eternity@unimi.it