Early Stage Researcher (ESR/PhD) in the Marie Skłodowska-Curie ITN European Training Network “TRANSMIT – TRANSlating the role of Mitochondria in Tumorigenesis” (H2020-MSCA-ITN-2016) – ESR 9 (University of Bologna, Dept. FaBiT, Italy)
TRANSMIT - TRANSlating the role of Mitochondria in Tumorigenesis
The consolidation of the knowledge that cancer is not only a genetic, but also a metabolic disease, has led scientists to investigate the intricate metabolic plasticity that transformed cells must undergo to survive the adverse tumor microenvironment conditions, and the contribution of oncogenes and tumor suppressors in shaping metabolism. In this scenario, genetic, biochemical and clinical evidences place mitochondria as key actors in cancer metabolic restructuring, not only because these organelles have a crucial role in the energy and biosynthetic intermediates production but also because occurrence of mutations in metabolic enzymes encoded by both nuclear and mitochondrial DNA has been associated to different types of cancer. TRANSMIT aims to dissect the metabolic remodeling in human cancers, placing the focus on the role of mitochondria and bridging basic research to the improvement/development of therapeutic strategies. Further, TRANSMIT fosters the communication of this emerging field to the patients and their families. To these aims, TRANSMIT will create a network of seven different countries, among which world-leading basic science and clinical centers of excellence, several industrial partners with up-todate omics technologies, as well as non-profit foundations and associations who care for cancer patients. By creating the critical mass of scientific excellence, TRANSMIT will allow to transfer the current knowledge into the wide field of cancer research, translating scientific and technical advances into the education and training of eleven Early Stage Researchers. TRANSMIT will implement training-through-research dedicated to unravel the metabolic features of cancer, as well as to provide a full portfolio of complementary skills through the creation of a network of basic, translational and industrial laboratories, devoted to a multidisciplinary/multisectorial education of young scientists.
1) Job Summary. The candidate will be enrolled in a PhD program to work in cellular and molecular biology, learning and exploiting biochemical, molecular and biology techniques. Starting from the knowledge of the interplay between respiratory complex I and HIF1a, the candidate will investigate how the unbalance of αKG/SA ratio can mimic a normoxic condition causing HIF1α destabilization, and thus, prevents hypoxic adaptation and metabolic reprogramming. In collaboration with other consortium partners and through secondments, the candidate will acquire knowledge of specific techniques to tackle the issues proposed. Collateral skills will be developed during the 3-year fellowship, such as grant and paper writing, fund raising abilities, outreach and dissemination in the field of molecular oncology.
2) Job description: Application refers to an Early Stage Researcher (ESR) position to be trained for 36 months at the Department of Pharmacy and Biotechnology, University of Bologna, in the framework of the TRANSMIT project entitled “Inducing pseudonormoxia as adjuvant therapeutic strategy for cancer” (ESR 9). Supervisor: Prof. Anna Maria Porcelli.
It has been demonstrated that complex I-defective cancer cells display an increased α-KG/SA ratio that activates PHDs and leads to a pseudonormoxic state where HIF1α is destabilized even during hypoxia. Thus, CIdeficient cancer cells are not able to acquire a HIF1α-dependent Warburg profile and their tumorigenic potential is markedly inhibited both in vitro and in vivo. These findings highlight a functional link between HIF1α stabilization and mitochondrial function opening to new therapeutic approaches for most solid cancers. Hence, the idea of a metabolic-based approach as adjuvant therapy represents a promising strategy against cancer, whose malignant progression is supported by adaptation to a hypoxic environment. In this context, ESR will prove that cell-permeable α-KG ester derivatives prevent tumor progression by inducing a pseudonormoxic state specifically in cancer cells. To achieve this goal, ESR will collect a panel of cancer and non-cancer primary cell lines deriving from the same tissue. Since 2D monolayer cell cultures are not representative of the complexity of 3D solid tumors, ESR will generate 3D culture models that will be characterized in terms of mitochondrial function, HIF1α status and tumorigenic features in vitro. Then, the toxicity of an already available library of fifteen cell-permeable α-KG ester derivatives will be evaluated. The effect of these compounds on PHDs activity and HIF1α stabilization and activation will be determined. Moreover, ESR will prove the ability of α-KG derivatives previously selected to modulate xenografts formation after injection of cancer cell lines in nude mice.
3) Subject area of PhD program in which the ESR will be enrolled and PhD program duration: Biological, Geological and Agricultural Sciences; PhD in Cellular and Molecular Biology (duration 3 year)
4) Host University that will provide the PhD degree: Università di Bologna, Italy- Department of Pharmacy and Biotechnology.
5) PhD program starting date: November 1st 2017
Required Educational Level
Degree: Degree/Master Degree in Biology, Biochemistry and Biotechnology
Degree Field: Human Cellular and Molecular Biology, Human Biochemistry, Human Molecular Genetics
Skills: Proven working experience in a research lab, proficiency in basic techniques in biochemistry, cell and molecular
Languages: Applicant should be fluent in written and spoken English
Applications, in English, should include CV, detailed academic transcripts, the abstract of the thesis (300 words max), a motivation letter, a reference letter and the application form, which are all to be submitted by email to Prof. Anna Maria Porcelli (firstname.lastname@example.org). Applicants are required to indicate both the title and the number of the project as the object of the e-mail (they are both mentioned in the "Job description" section).
Application deadline: June 18th 2017
The application form can be download from the following webpage: https://euraxess.ec.europa.eu/jobs/199746 by clicking on the "WHERE TO APPLY” section.
The applicant may be a national of a Member State, of an Associated Country or of any other Third Country.
Career: At the time of recruitment, applicants are to have academic qualifications to access a PhD position and have to be in their first four years of their research careers and have not been awarded with a doctoral degree.
Applicants are required to have less than 4 years of full time research experience.
Mobility: At the time of recruitment, Applicants must not have resided in Italy for more than 12 months in the 3 years immediately prior to the recruitment date and not have carried out their main activity (work, studies, etc.) in that country.
· Enrollment in a PhD school in a specific area
· The selected candidate will be appointed under a 36-month full-time employment contract according to the Italian national legislation. The remuneration will be compliant with the rules of the ITN-MSCA Program. The gross amount for the benefit of the researcher includes:
a) Monthly living allowance: the amount is € 3,318.37 per month.
b) Mobility allowance: the amount is € 600,00 per month (€ 7.200,00/year).
c) Family allowance: a Family allowance of €500 per month will be paid to researcher with family. Family” is defined as persons linked to the researcher by (i) marriage, or (ii) a relationship with equivalent status to a marriage recognised by the national or relevant regional legislation of the country where this relationship was formalised; or (iii) dependent children who are actually being maintained by the researcher. The family status of a researcher will be determined at the time of their (first) recruitment in the project and will not evolve during the project lifetime.
The net amount results from deducting all compulsory social security contributions as well as direct taxes from the gross amount.
· A highly multidisciplinary, cross-cultural and competitive training program in the field of metabolism in cancer and molecular oncology
· Secondments and a specific training program
· Vacation days/year: 30 days/year in addition to November 1, December 8-25-26, January 1, 6, April 25, May 1, June 2. Easter and Easter Monday (they change each year)
First selection step: Curriculum evaluation. Numerical scores will be awarded for grading criteria such as study marks, duration of study, scientific publications in peer reviewed journals, reference letters. Only the admitted candidates will be contacted by e-mail for the second selection step.
Second selection step: Skype or face-to-face interview in which candidates will give a short presentation of their master thesis and of a scientific paper that they will receive three weeks before the interview.
Two weeks during September / October 2017