Cellular senescence

Title: Functionalized nanomaterials for targeting and clearance of senescent cells as a new tool in precision medicine

Supervisor: dr hab. Anna Lewińska, prof. UR, e-mail: alewinska@ur.edu.pl

                     Department of Biotechnology, Institute of Biology and Biotechnology, College of Natural Sciences, University of Rzeszow, Pigonia 1, 35-310 Rzeszow, Poland

Short description:

Cellular senescence, a state of permanent cell cycle arrest and increased secretion of proinflammatory factors, is a complex phenomenon that may contribute to different biological outcomes such as tumor suppression, tumor promotion, aging and tissue repair. Thus, senescent cells may promote both beneficial effects by proinflammatory response-mediated recruitment of immune cells to eliminate damaged cells and stimulation of proliferation and differentiation of neighboring cells (tissue remodeling) and protection against propagation of damaged dysfunctional precancerous cells (inhibition of tumorigenesis) and detrimental effects by chronic inflammation (induction of tumorigenesis and aging). Effective strategies to eliminate the harmful effects of the presence of senescent cells (SCs) are currently being investigated. Additionally, a significant number of commonly used anticancer therapies have been shown to stimulate cellular senescence in neoplastic and/or non-neoplastic tissues, which is now defined as another side effect of the anticancer treatment. The senescence-associated secretory phenotype (SASP) is considered a key factor in promoting the growth of neoplastic tissue. It has been proven that pro-inflammatory factors produced by senescent cells (normal and neoplastic) can promote cancer cell proliferation, migration, invasiveness, angiogenesis, and epithelial-mesenchymal transition (EMT). The elimination of senescent cells is called senolysis. Senolysis may be a part of one of the promising anticancer strategies of modern medicine, especially when combined with more traditional cancer interventions. Many anticancer drugs have been shown to be senolytic to tumor cells and to normal cells when used in specific concentrations, alone or in combination with others. The aim of the PhD project will be a construction of intelligent and safe nano-carriers for improved bioavailability and specificity of senolytics/senostatics for senescent neoplastic cells.

Adamczyk-Grochala J, Lewinska A. Nano-Based Theranostic Tools for the Detection and Elimination of Senescent Cells. Cells. 2020 Dec 10;9(12):2659. doi: 10.3390/cells9122659.

Requirements:

• Previous experience in all or some of the following: cancer research, cell biology, protein expression and analysis, flow cytometry, microscopy, and statistical analyses.
• Applicants should be highly motivated, able to work both independently and in collaboration (as a part of the team), inventive and communicative.
• Fluency in both written and spoken English is mandatory.