PRR Project

Summary

The selected candidate will be expected to bring strong and innovative research value to reinforce the scientific interests and strategy of the Cancer integrative program of i3S. Applicants must hold a PhD in Health/Life Sciences, or related areas for 5 or more years, an excellent scientific track record, and are expected to contribute to the mission of i3S by: a) contributing to develop highly innovative research projects in basic, translational and clinical research in life and health sciences, in the framework of Cancer integrative program research groups; b) promoting knowledge and technology transfer; c) supporting advanced training by participating in graduate and PhD programs, supervising PhD, Master and other students, and by promoting advanced training courses; and  d) increasing science awareness by participating in the i3S educational program and outreach activities.The Cancer Program at i3S aims to understand cancer biology and translate it into practical benefits for patients. To reach this goal, the Cancer Program integrates research groups aiming to understand fundamental biological processes that, when dysregulated, contribute to the biological properties acquired by cancer cells during the process of tumorigenesis, described as “Cancer Hallmarks”. To empower its research environment and generate critical mass in basic research in cancer biology, the Cancer Program requests that this Assistant Researcher position will be attributed to an outstanding candidate working in one or more of the strategic areas related to diverse Cancer Hallmarks. 1) Sustaining Proliferative Signaling: the cell cycle control is a key mechanism, governing cells´ orderly progression through growth, replication, and division phases to ensure accurate proliferation and genetic information transfer to daughter cells. Understanding how cells coordinate cell cycle progression, which checkpoints contribute to the proper progression and how the status of important structures of a dividing cell (e.g kinetochores) contribute to this control is essential. Also, during mitosis, the molecular mechanisms behind chromosome segregation fidelity are active, therefore, characterizing how chromosome segregation is regulated and how mitotic failure may lead to aneuploidy is vital to understand cancer. Among several key players in cell cycle, there are motor proteins required for centrosome separation and chromosome movements, that are key to understand chromosome stability and, when disrupted, tumor progression. Recent evidence underscores aberrant cytokinesis in aneuploidy induction, aiding cancer development; thus, studying this late mitotic phase is crucial for cancer comprehension. 2) Invasion and Metastasis: the identification of the mechanisms that control cell polarity during and after cell division, whose disruption often leads to the ability of cells to invade surrounding tissues and to create metastasis, is fundamental to understand tumor progression. 3) Evading Growth Suppressors: cell growth, impacted by signaling alterations, is finely tuned during normal organ development, making it an important mechanism to study. Importantly, some signaling pathways can influence the cytoskeleton to adjust cell shape to cancer cell behaviors, which in turn control autonomous cytoskeleton-mediated signal, a feedback loop important to understand cancer initiation and progression. 4) Genome Instability and Mutation: chromosomal rearrangements and genomic instability can lead to tumor development. Understanding which alleles, common or rare, are present in a population and whose can predispose to cancer development or other cancer-susceptible diseases, is fundamental to understand the trigger of cancer and to improve cancer risk prediction. Additionally, many mutations are not yet well understood, in particular the ones affecting the non-coding genome. These mutations can affect transcribed but untranslated regions of DNA, impacting in RNA processing and gene activity. Cis-regulatory elements are also fundamental for proper tissue specific expression of genes and cellular response. Profiling and determining which cis-regulatory elements might be relevant for cancer trigger and progression is fundamental. 5) Finally, several hallmarks of aging, as genomic instability, prone to cancer, while other features (e.g stem cell exhaustion) suppress oncogenesis. Therefore, understanding aging is vital, in particular addressing the mechanisms of genomic instability contributing to aging and age-related diseases, as well as understanding main players in cell senescence, as cellular stress modulators and cellular clearance mechanisms.