Albert Einstein | EPFL Graph Search

'Albert Einstein' (ˈaɪnstaɪn ; ˈalbɛʁt ˈʔaɪnʃtaɪn; 14 March 1879 – 18 April 1955) was a German-born theoretical physicist, widely held to be one of the greatest and most influential scientists of all time. Best known for developing the theory of relativity, he also made important contributions to quantum mechanics, and was thus a central figure in the revolutionary reshaping of the scientific understanding of nature that modern physics accomplished in the first decades of the twentieth century. His mass–energy equivalence formula E = mc2, which arises from relativity theory, has been called "the world's most famous equation". He received the 1921 Nobel Prize in Physics "for his services to theoretical physics, and especially for his discovery of the law of the photoelectric effect", a pivotal step in the development of quantum theory. His work is al

Insight into the Regulation of Telomerase Access to Telomeres by Shelterin Proteins

Elena Aritonovska

Recruitment to telomeres is a pivotal step in the function and regulation of human telomerase. Impaired telomerase function can lead to premature organismal aging, development of cancer and multisystem disorders such as dyskeratosis congenita. Telomerase access to telomeres may be regulated by a telomere-binding complex termed shelterin, which is composed of TRF1, TRF2, RAP1, TIN2, TPP1 and POT1 proteins. However the molecular basis for human telomerase recruitment to telomeres is not known. Here, we have directly investigated the process of telomerase recruitment via chromatin immunoprecipitation (ChIP) and fluorescence in situ hybridization (FISH). We find that depletion of two components of the shelterin complex – TPP1 and the protein that tethers TPP1 to the complex, TIN2 – results in a loss of telomerase recruitment. On the other hand, we find that the majority of the observed telomerase association with telomeres does not require POT1, the shelterin protein that links TPP1 to the single-stranded region of the telomere. Furthermore, we find that the double-stranded telomere binding protein, TRF2 is dispensable for telomerase association with telomeres. Deletion of the oligonucleotide/oligosaccharide-binding fold (OB-fold) of TPP1 further disrupts telomerase recruitment. In addition, while loss of TPP1 results in the appearance of DNA damage factors at telomeres, the DNA damage response per se does not account for the telomerase recruitment defect observed in the absence of TPP1. Our findings indicate that TIN2-anchored TPP1 plays a major role in the recruitment of telomerase to telomeres in human cells and that the recruitment does not depend on POT1 or interaction of the shelterin complex with the single-stranded region of the telomere. We propose that the loss of TRF2 can be compensated by the second double-stranded telomere binding protein, TRF1 that anchors TIN2/TPP1-recruited telomerase onto the telomeres. Dyskeratosis congenita (DC) is a multisystem disorder characterized with bone marrow failure, cancer predisposition and defective telomere maintenance. The TINF2 gene that encodes for the TIN2 shelterin protein is one of seven mutated genes identified in DC patients. Here, we have examined the effects of TIN2 DC mutants on telomere protection and shelterin protein stability. We find that exogenous expression of TIN2 DC mutants can rescue the TIN2-depleted phenotype, restoring TPP1 protein levels and telomere protection. Our findings indicate that TIN2 DC mutants preserve the intact telomere structure and protection. We propose that defective telomere elongation may be the underlying cause of impaired telomere maintenance in TIN2 DC patients.

EPFL2011

Advanced gravitational lensing techniques for precision cosmology

Markus Rexroth

Gravitational lensing - the deflection of light by gravity - has greatly developed since its famous first observation in 1919, which validated Einstein's General Theory of Relativity. The strength of this effect does not depend on the nature of the mass which produces the gravitational field and thus it is a great tool to weigh both the visible and the invisible parts of the universe. Consequently gravitational lensing has become a pillar of observational cosmology over the last decades, and it is used to study the nature of Dark Matter and Dark Energy, the two mysterious quantities which dominate our universe, but are not yet understood by physics theory. The success of this endeavor rests on a thorough understanding of lensing theory and observations, including their systematics, the availability of a sufficient amount of precise data, and the development of efficient software to precisely measure these lensing effects in digital astronomical images. This thesis presents advanced techniques which can improve several of these areas. In the first part, we develop a new theoretical method to break the mass-sheet degeneracy, which prevents accurate mass determinations from lensing observations. The second part focuses on spectroscopic data from MUSE, a second-generation Integral-Field Spectrograph installed on one of the largest ground-based telescopes on earth. We present a pipeline which permits the efficient determination of the redshift of a source observed by MUSE. The redshift indicates the distance of the source from us and depends on the expansion of the universe. In addition, we use MUSE observations of a galaxy cluster to improve the determination of its total weight, including the dominant Dark Matter component. In the third part of this thesis, we investigate how we can accelerate the computation of these mass maps. In the era of big data and large surveys, computing efficiency is key to obtaining new scientific insights. We use High Performance Computing techniques like graphics card acceleration to improve the code performance and we develop a method which harnesses extra performance from using single precision without loosing the required accuracy. In the last section, we present first results from measuring flexion, a higher order lensing effect which could substantially increase the resolution of lensing mass maps and thus lead to a sharper view of structure in the universe.

EPFL2018

Advanced gravitational lensing techniques for precision cosmology

Markus Rexroth

EPFL2018

Insight into the Regulation of Telomerase Access to Telomeres by Shelterin Proteins

Elena Aritonovska

EPFL2011