Gastgeber: R. J. Dwayne Miller

Ming Lei - Capping the Ends: Structure and Function of Telomere Proteins

MPSD Seminar
Telomeres, the natural ends of linear eukaryotic chromosomes, are specialized protein-DNA complexes that play essential roles in cell viability and genome integrity. The long-term goal of my research is to understand how telomeres protect chromosome ends and mediate their replication by telomerase. A six-protein complex, called shelterin, associates with telomeres and protects the ends of human chromosomes. A major gap in our knowledge of the shelterin complex is how its protein components organize at telomeres. I will present our recent studies that reveal the molecular architecture and functional significance of the shelterin complex. [mehr]
Spectroscopic mapping by STEM/EELS has proven to be a powerful technique for determining the structure, chemistry and bonding of interfaces, reconstructions, and defects. So far, most efforts in the physical sciences have focused on room temperature measurements where atomic resolution mapping of composition and bonding has been demonstrated [1-3]. For many materials, including those that exhibit electronic and structural phase transitions below room temperature and systems that involve liquid/solid interfaces, STEM/EELS measurements at low temperature are required. Operating close to liquid nitrogen temperature gives access to a range of emergent electronic states in solid materials and allows us to study processes at liquid/solid interfaces immobilized by rapid freezing [4,5]. [mehr]

Liquid-Phase Electron Microscopy of Cells and Nanomaterials in Liquid

MPSD Seminar
Transmission electron microscopy (TEM) has traditionally been associated with the study of thin solid samples in vacuum. With the availability of reliable thin membranes of silicon nitride, TEM of liquid specimens has become accessible with nanoscale resolution in the past decade [1]. The usage of scanning transmission electron microscopy (STEM) presents a novel concept to study membrane proteins within whole mammalian cells in their native liquid environment [2]. The cells in liquid are placed in a microfluidic chamber enclosing the sample in the vacuum of the electron microscope, and are then imaged with STEM. It is not always necessary to enclose the cells in the microfluidic chamber. For many studies, it is sufficient to obtain information from the thin outer regions of the cells, and those can be imaged with high resolution using environmental scanning electron microscopy (ESEM) with STEM detector [3]. A third option is to cover a liquid specimen under a thin membrane of graphene providing the thinnest possible layer [4]. Liquid STEM was used to explore the formation of HER2 homodimers at the single-molecule level in intact SKBR3 breast cancer cells in liquid state [3]. HER2 is a membrane protein and plays an important role in breast cancer aggressiveness and progression. Data analysis based on calculating the pair correlation function from individual HER2 positions revealed remarkable differences its functional state between rare- and bulk cancer cells with relevance for studying the role of cancer cell heterogeneity in drug response. We discovered a small sub-populations of cancer cells with a different response to a prescription drug [5]. Liquid STEM was also used to explore the behavior of nanoparticles in liquid in time-lapse experiments. It was discovered that nanoparticle movement in close proximity of the supporting silicon nitride membrane was three orders of magnitude slower than what was expected on the basis of Brownian motion for a bulk liquid [6], pointing to the existence of a layer of highly ordered liquid at the membrane. References [1] de Jonge, N. and Ross, F.M. Nat. Nanotechnol., 6, 695-704 (2011) [2] de Jonge, N., et al. Proc. Natl. Acad. Sci., 106, 2159-2164 (2009) [3] Peckys, D.B., et al. Sci. Adv., 1, e1500165 (2015) [4] Dahmke, I.N., et al. ACS Nano, 11, 11108-11117 (2017) [5] Peckys, D.B., et al. Mol. Biol. Cell, 28, 3193-3202 (2017) [6] Verch, A., et al. Langmuir, 31, 6956–6964 (2015) [mehr]
Zur Redakteursansicht