Integrated Calendar

In this talk, I will review recent work by myself and others on Jewish population and medical genetics, focusing on Ashkenazi Jews (AJ). I will describe the mixture events of AJ in Europe, the founder event they have experienced in the late Middle Ages, and their connections to ancient populations of the Levant. I will then describe large-scale genomic databases that we have recently generated for AJ, and the opportunities they open in medical genetics given the unique AJ demographic history. I will describe a few medical genetics projects including carrier screening, genome-wide association studies of microbiome composition and other traits, and preimplantation genetic diagnosis.

Proteins are dynamic entities and function is often related to motions on time-scales from picoseconds to seconds. Understanding not only the backbone, but also the dynamics and interactions of side chains and ions within proteins is crucial, because side chains cover protein surfaces and are imperative for substrate recognition and both side chains and ions are key for most active sites in enzymes.
New NMR-based methods, anchored in 13C-direct-detection, to characterise the motions and interactions of functional side chains in large proteins will be presented. One class of experiments is aimed at arginine side chains and allows the strength of interactions formed via the guanidinium group to be quantified. NMR measurements of the solvent exchange rate of labile guanidinium protons as well as measurements of the rotational motion about the Nε-Cζ bond allows for such quantifications. Secondly, a new class of NMR experiments is presented, which relies on 13C-13C correlation spectra and allows a general quantification of motion and structure of side chains in large proteins. The new 13C-13C correlation spectra are applied to a 82 kDa protein, where well-resolved spectra with minimal overlap are obtained within a few hours.
NMR-based methods to characterise potassium binding in medium-large proteins will also be presented. Due to its size, 15N-ammonium can be used as a proxy for potassium to probe potassium binding in medium-large proteins. NMR pulse sequences will be presented to select specific spin density matrix elements of the 15NH4+ spin system and to measure their relaxation rates in order to characterise the rotational correlation time of protein-bound 15NH4+ as well as report on chemical exchange events of the 15NH4+ ion.

Abstract

With the advent of novel fabrication techniques in the 1980s and 1990s, it became possible to explore many physical phenomena at the nanoscale. Since then, a lot of progress has been done in the understanding of the electronic transport, mechanical, and optical properties of nanoscale devices. However, thermal transport in these systems has remained relatively unexplored because of the experimental difficulty to measure the flow of heat and energy at this small scale. In this talk, I will review our theoretical and experimental efforts to establish the fundamental laws that govern nanoscale thermal transport by using atomic and molecular junctions as a playground. In particular, I will discuss basic phenomena such as Joule heating and Peltier cooling in molecular junctions [1,2] and quantized thermal transport in atomic-size contacts [3].

References

[1] W. Lee, K. Kim, W. Jeong, L.A. Zotti, F. Pauly, J.C. Cuevas, P. Reddy, Nature 498, 209 (2013).
[2] L. Cui, R. Miao, K. Wang, D. Thompson, L.A. Zotti, J.C. Cuevas, E. Meyhofer, P. Reddy, Nature Nanotechnology 13, 122 (2018).
[3] L. Cui, W. Jeong, S. Hur, M. Matt, J.C Klöckner, F. Pauly, J.C. Cuevas, E. Meyhofer, P. Reddy, Science 355, 1192 (2017).

A new type of transmission electron microscopes operating at electron energies between 80keV and 20keV has been developed to obtain structural and electronic properties of advanced low-dimensional material at the atomic scale. It allows to undercut most of the materials knock-on damage thresholds and enables sub-Angstroem resolution in an 4000x4000 pixels, single-shoot image down to 40keV by correcting not only the geometrical aberrations of the objective lens but also its chromatic aberration. During the imaging process, the interaction of the beam electrons with the low-dimensional material can, nevertheless, results in changes of the atomic structure due to ionization and radiolysis, and sophisticated sample preparation methods are employed to reduce these effects. In this talk, we briefly outline key instrumental and methodological developments and report on structural properties of low-dimensional materials. We not only determine the structure of the pristine material but also use the electron beam to engineer defined properties. Thus, we show for instance the dynamics of extended defects in MoTe2 and WS2 and the creation of a commensurate charge density wave (CDW) in a monolayer 1T-TaSe2, as well as properties of MnPS3, and moreover the dynamics and bond order changing of dirhenium molecule in single-walled carbon nanotubes. Finally we intercalate bilayer graphene by lithium and study in-situ lithiation and delithiation between bilayer graphene, identify single Li atoms as well as the structure of the new high density crystalline Li- phase.

Activity-dependent modifications to synaptic connections – synaptic plasticity – is widely believed to represent a fundamental mechanism for altering network function. This belief also implies, however, that synapses, when not driven to change their properties by physiologically relevant stimuli, should retain these properties over time. Otherwise, physiologically relevant modifications would be gradually lost amidst spurious changes and spontaneous drift. We refer to the capacity of synapses to maintain their properties over behaviorally relevant time scales as 'synaptic tenacity'.

The seminar will examine the challenges to synaptic tenacity imposed by the short lifetimes of synaptic molecules, their inherent dynamics and the logistics of replenishing remote synapses with these molecules at appropriate amounts and stoichiometries. It will then examine the effects these processes have on the (in)stability of synaptic properties , on synaptic size configurations and distributions and on the scaling of these distributions. Finally, it will compare the magnitudes of synaptic changes driven by these processes to those of changes driven by deterministic, activity-dependent synaptic plasticity processes.