לוח שנה משולב

We investigate theoretically a model system of colloids in water. The colloid size is neither very small compared to the Debye length, nor very large. We look at the orientation of the colloid near a surface, and find bistable behavior. This may have implications for flow in microfluidic channels, and for crystallization near surfaces.

Glycans are ubiquitous in nature and participate in a wide variety of biological processes, that span from mediating cell-cell interactions to modulating protein stability and folding. Glycan involvement in diverse biological functions can be rationalized by the equally extensive potential for structural diversity. They vary not only in monosaccharide composition and primary sequence, like proteins and nucleic acids, but also the monosaccharides can vary in ring sizes, linkage types, and functional group modifications. Therefore, their structural complexity has the potential for encoding a myriad of functions. However, it is this “structural richness” that hampers progress in stablishing structure-function relationships, simply because tools and strategies for structure determination are lacking.
We are delineating three-dimensional glycan solution structure to gain insight into how they function, which should facilitate development of glycan-based vaccines, drug delivery systems, and antibiotics of the future. To this end, we use heteronuclear multidimensional NMR to determine conformations and dynamics of 15N, 13C enriched oligo- and polysaccharides. We have detected interresidue hydrogen bonds and used RDCs to delineate the relative orientations of the rigid monosaccharide building blocks. However, RDC measurements are fraught with errors from strong coupling effects. Thus, we have developed methods to accurately measure one-bond 1H-13C splittings and 13C-13C splittings as well as RDCs. I will illustrate the application of these methods for bacterial polysaccharide model systems and show how we applied them to support the two-residue per turn helical structure of 2-8 tetrasialic acid and the smaller conformationally stable dimer in solution at low temperatures.

Observations and climate simulations show that polar regions warm faster than the rest of the globe in response to radiative forcing. Feedback diagnostics in models show that a large fraction of this enhanced polar warming is due to strong positive lapse-rate feedback. However, there is little mechanistic understanding for why this feedback is positive and what controls its strength. Here, I discuss a mechanism for high-latitude lapse rate feedback and show it functioning in a set of simplified GCM simulations. The mechanism hinges crucially on low cloud response. In this sense, high-latitude lapse-rate feedback is a cloud feedback in disguise.

DNA is an amazing memory device that holds the operating system of life. However, DNA sequencing fails to extract the full range of information associated with genetic material and is lacking in its ability to resolve variations between genomes. As a consequence, many genomic features remain poorly characterized in the human genome reference. In addition, the information content of the genome extends beyond the base sequence in the form of chemical modifications such as DNA methylation or DNA damage lesions that chemically encode our life experiences in our DNA. By applying experimental principles of single molecule detection we gain access to the structural variation and long range patterns of genetic and epigenetic information. We show how physical extension of long DNA molecules on surfaces and in nanofluidic channels reveals such information in the form of a linear, optical “barcode” showing distinct types of observables. Recent results from our lab demonstrate our ability to detect epigenetic marks and various forms of DNA damage on individual genomic DNA molecules and use this information for medical diagnostics.