The Axe Santé is organising a Health Tech Lunch on Tuesday 3rd May from 10:30 to 11:45 at Energypolis in Sion (room N208).
Joachim Lingner obtained his PhD (1992) at the Biozentrum of the University of Basel in the laboratory of Walter Keller studying the 3’ end formation of messenger RNAs. During his postdoctoral work (1993-1997) with Thomas Cech at the Howard Hughes Medical Institute of the University of Colorado at Boulder, Lingner discovered the catalytic subunit of telomerase (TERT) which counteracts telomere shortening and cellular senescence in cancer cells, stem cells and the germ line. Since 1997, Lingner is group leader at ISREC and since 2005 professor at the EPFL in Lausanne, Switzerland. The Lingner lab studies how telomeres enable chromosome stability and how they are maintained to regulate cellular lifespan. The team elucidated how the telomerase enzyme is regulated at chromosome ends to counteract telomere shortening. The lab also discovered that telomeres are transcribed into long the long noncoding RNA TERRA, which regulates telomeric chromatin structure and telomere maintenance by telomerase and homology directed repair. Finally, his team developed techniques to purify telomeric chromatin and determine its protein composition by mass spectrometry to uncover the changes that occur in the telomeric proteome during aging and disease including cancer. Lingner obtained a START-fellowship from the Swiss National Science Foundation (1997), the Friedrich Miescher prize (2002), an ERC advanced investigator award (2008) and is an elected member of EMBO (2005) and the Academia Europaea (2020).
Telomeres and Telomerase: Roles During Cancer and Aging
Telomeres correspond to the physical ends of eukaryotic chromosomes. Telomeric DNA consists of 5’-TTAGGG-3’ tandem repeats with an overall length of 3,000 to 15’000 base pairs. Telomeres ensure chromosome stability protecting chromosome ends from degradation and chromosome rearrangements which are typically seen in cancer. Telomeres have also crucial tumor suppressive function. They provide a molecular clock and limit the replicative potential of normal somatic cells. In somatic cells, telomeres shorten with every round of DNA replication. When telomeres reach a critically short size, they trigger a signaling cascade known as DNA damage response, which induces cellular senescence. Senescent cells display permanent growth arrest. Thus, premalignant cells that have lost growth control hit the senescence barrier before they can form large and life-threatening tumors.
During tumorigenesis, however, senescence is overcome through loss of the DNA damage response often involving mutations in the tumor suppressors p53 and pRB. Proliferation of such premalignant cells may then continue until the cells reach a state referred to as cell crisis. Cell crisis is characterized by a nearly complete erosion of telomeres. Telomere-deprived chromosome ends become substrates for DNA repair activities which normally reseal accidental chromosome breaks. When active at eroded chromosome ends, however, the repair will lead to chromosome end-to-end fusions. Fused chromosomes are frequently mis-segregated during mitosis and they break, causing rampant genome instability and cell death. Only extremely rare cells can survive cell crisis. In most cases, the surviving cells acquired additional mutations which activate an enzyme called telomerase. Telomerase elongates the shortened telomeres reestablishing their length and function. Through telomerase expression, cancer cells acquire an immortal phenotype. Cell immortality represents one of the cancer hallmarks.
As described above, telomere shortening in somatic cells is very important to reduce the risk of cancer development. On the other hand, telomere shorting may contribute to tissue exhaustion in highly proliferative organs during human aging. It seems, that an optimal telomere length early in life must have evolved to balance between the risks of cancer and tissue dysfunction during aging.
Registration : https://doodle.com/meeting/participate/id/bo2Xny3a/vote