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 evidence places 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 mutations in metabolic enzymes encoded by both nuclear and mitochondrial DNA have been associated with 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 meet these aims, TRANSMIT has formed a network throughout seven countries, and consisting of 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 a critical mass of scientific excellence, TRANSMIT will allow transfer of 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 unraveling the metabolic features of cancer, as well as providing 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: Within the training program provided by the TRANSMIT consortium, the candidate will have his/her training at the Karolinska Institutet, Sweden, and will be employed there as a Research Assistant, but will be enrolled as a PhD student in the 3-year PhD program in General Medical Sciences at the University of Bologna (UNIBO), Italy. UNIBO will thus provide the envisaged PhD degree.
The candidate will in a research lab environment design and carry out analyses of mitochondrial involvement and function in cancer-related clinical samples as well as in cultured cells in vitro, and relate the results to clinically and biologically relevant factors such as patient outcome data and mechanisms of chemoresistance. Lab work includes setting up routines for sample handling, cell cultures and performing cell-based assays. The candidate will also contact and interact with clinicians, pathologists, companies, biostatisticians etc. The tasks thus include thorough and rational planning, monitored by supervisor(s), accurate and neat hands-on work in the lab, and clear presentation of results. The program also includes courses and secondments with other members of the TRANSMIT network. As science and knowledge are based on communicable data and ideas, organizational as well as communication skills will be emphasized and further trained. The candidate will be required to spend a six-month period in Italy.
2) Job description: Ovarian cancer (OC) is the deadliest gynecological cancer, making it the fifth leading cause of cancer deaths in women. Even if treatment (surgery + platinum-based chemotherapy) is initially successful, many patients relapse within 6 months into disseminated disease; highly chemoresistant so-called cancer stem cells are believed to underlie this development. Risk factors include obesity and/or diabetes type 2 (DM2). Both have been associated with increased risk as well as poorer outcome and survival in OC. Risk and/or poorer outcome appear to involve altered levels of cyto- and adipokines secreted by obese adipose tissue. See review by Craig et al., Gyn Oncol 2016.
The candidate will examine: (a) molecular mechanisms of resistance to platinum chemotherapy in cultured OC cells, with focus on how mitochondria and cellular metabolism differ in resistant and sensitive cells, e.g., mitochondrial morphology and dynamics, and which metabolic pathways are involved in platinum resistance and/or cancer stem cell features; (b) the role(s) of regulators of mitochondrial biogenesis and function, e.g., the transcriptional co-regulator PGC1, in regulation of metabolism, chemoresistance and/or cancer stem cell features in OC, e.g., using in vitro knockdown of expression; (c) effects of selected cytokines and adipokines on mitochondria and chemoresistance in cultured OC cells, and correlation of cyto-/adipokine levels in patient samples with clinical data such as clinical resistance, survival time, BMI etc; (d) expression levels of PGC1 and presence of cancer-associated adipocytes in patient samples, and correlations with clinical data.
Lab methods include western blotting, ELISAs, PCR methods, cellular viability assays, metabolic assays (e.g., ATP measurements, oxygen consumption, lactate production) and metabolic marker profiling, confocal microscopy, knockdown methods, immunohistochemistry. Results are expected to be of publication quality.
Communication skills are practiced under supervision in the form of manuscript writing, poster presentations, student seminars and all other types of interaction with other professionals and students. Courses include Oncology and Tumor Biology comprising both clinical and preclinical knowledge, Biostatistics and 1-2 courses of the candidate´s choice in consultation with the supervisor.
The profile of the research environment of the Department of Oncology-Pathology at the Karolinska Institutet is translational, i.e., it supports the translation of preclinical research into clinically useful knowledge. The research group of Dr. Shoshan has a long-standing interest in cancer cell metabolism and tumor progression, and collaboration with clinicians, pathologist as well as biostatisticians. The Department will in the spring of 2018 move to new premises built to promote interaction between different research groups and interests.
3) Subject area of PhD program in which the ESR will be enrolled and PhD program duration: PhD in General Medical Sciences – 3 years
4) Host University that will provide the PhD degree: Department of Medical and Surgical Sciences - University of Bologna, Italy
5) PhD program starting date: November 1st 2017
Required Educational Level
Degree: An M.Sc. degree in Biomedicine or similar Life Science discipline, with emphasis on Cell Biology or Tumor Biology, also a good grounding in Biochemistry.
Degree Field: Biomedicine or similar Life Science discipline, with emphasis on Cell Biology or Tumor Biology, also a good grounding in Biochemistry.
Skills: Excellent communication skills
Languages: Applicant should be fluent in written and spoken English
Applications, in English, should include a CV, detailed academic transcripts in the form of certified copies of all undergraduate level certificates, a certified copy of the M.Sc. thesis or similar, a list of research-related methodological skills that the applicant is proficient in, a list of training experiences abroad (e.g. Erasmus project, Mobility fellowship, Leonardo project), a motivation letter and a reference letter, which are all to be submitted by email to Dr. Maria Shoshan, at firstname.lastname@example.org
Application deadline: June 30th 2017
*Eligibility: The applicants must be in possession of a degree in Biomedicine or similar Life Science disciplines at the date of recruitment at the date of recruitment - an ‘early stage researcher’ (i.e. in the first four years of his/her research career and not have a doctoral degree).
The applicant may be a national of a Member State, of an Associated Country or of any other Third Country.
The applicants may not have resided in the country where the research training activities take place (i.e. not in Sweden) for more than 12 months in the 3 years immediately prior to the recruitment date and may not have carried out their main activity (work, studies, etc.) in that country.
· Enrollment in a PhD school in a specific area
· 3-year employment contract: taxable salary (SEK 25,800/month + €600/month converted to SEK at payment) for 36 months that entitles to Swedish social security benefits.
· 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
· 25 vacation days/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: A Skype 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.
Third selection step: A face-to-face interview with the top two candidates. Travelling costs will be entirely at the candidates’ expense.