Integrated Calendar

During the seminar we will introduce latest developments in white light Spinning disk confocal technique as well as in active illumination. We will first demonstrate how structured light based spinning disk is giving a high resolution and high confocality solution. Images and movies of various biological samples will be presented.
We will also describe the recent developments in active illumination of which can be easily installed on each existing microscope and can be used in Photo-stimulation, uncaging, Ablation etc. We will present images and movies of typical Optogenetics experiments using the new DMD based Mosaic 3.
Link to systems:
Andor Revolution DSD: http://www.andor.com/microscopy-systems/revolution-dsd
Active Illumination: http://www.andor.com/microscopy-systems/active-illumination

Dephasing (decoherence) processes, converting coherent behavior to a classical one, are at the focus of intensive research. I'll describe a few experiments, performed in mesoscopic electronic systems, where dephasing is introduced by an artificial and well controlled environment ('path detector') - thus allowing a better understanding of such ubiquitous processes.

Pathogenic infections represent a persistent threat to human health. The rapid development of resistance to drug therapies creates a continuing need for developing new anti-infective agents. Host-Defense Peptides (HDPs) represent a potential source of inspiration for development of new antibacterial agents. These peptides are produced by eukaryotes as part of the innate immune response to bacterial infection. Elucidation of high-resolution structure has been challenging for the large group of HDPs that form helices on or within membranes but do not manifest a strong folding propensity in aqueous solution. We used racemic crystallization to obtain the crystal structure of an analogue of the widely-studied HDP, magainin 2. Ala8,13,18-magainin 2 is a designed variant that displays enhanced antibacterial activity relative to the natural peptide. The crystal structure of Ala8,13,18-magainin 2, features a dimerization mode that has previously been proposed to play a role in the antibacterial activity of magainin 2 and related peptides (1).
The broad molecular diversity among HDPs suggests that their prokaryotic-selective activity is not tightly coupled to specific features of amino acid sequence or peptide conformation. This situation has inspired the development of several families of sequence-random hydrophobic-cationic co-polymers that display antibacterial behavior with varying levels of hemolytic activity. We developed a new experimental approach for exploring the impact of sample diversity on the biological activity profiles of mixtures (2). Specifically, we employed solid-phase synthesis in an unconventional way to generate peptide mixtures that contain one type of hydrophobic residue and one type of cationic residue. Each mixture was random in terms of sequence, but highly controlled in terms of chain length and stereochemistry. Analysis of the antibacterial and hemolytic properties of these mixtures revealed that selective antibacterial activity can be achieved with heterochiral binary mixtures but not homochiral binary mixtures.
We have explored nylon-3 materials (poly--peptides) as functional mimics of HDPs (4, 5). Nylon-3 polymers are readily synthesized via ring-opening polymerization of -lactams; some hydrophobic-cationic copolymers display broad antimicrobial activity. It is challenging to perform structure-activity relationships studies for nylon-3 copolymers (or other copolymers) because each sample contains many different kinds of molecules (different lengths, different subunit compositions, different subunit sequences, different subunits stereochemistries). Using our unconventional solid-phase approach we were able to prepare nylon-3 copolymer mixtures that are better defined than are the mixtures generated via ring-opening polymerization of -lactams. This synthetic strategy is not available for any other types of polymers that have been reported to function as selective antibacterial agents. Our findings show that chain length and stereochemistry are important parameters in terms of determining the activity of polymers of this type.
1. Hayouka, Z. Chakraborty, S. Liu, R. Gellman, H.S. (2013). Interplay Among Subunit Identity, Composition, Chain Length and Stereochemistry in the Activity Profile of Sequence-Random Oligomer Mixtures. J. Am. Chem. Soc. 135(32):11748-5.
2. Hayouka, Z. Mortenson, D.E. Kreitler, D.F. Weisblum, B. Forest, K.T. Gellman, H.S. (2013). Evidence for Phenylalanine Zipper-Mediated Dimerization in the X-Ray Crystal Structure of a Magainin 2 Derivative. J. Am. Chem. Soc. In press.
3. Liu, R. Chakraborty, S. Hayouka, Z. Gellman, H.S. (2013). Nylon-3 polymer as antifungal agent. J. Am. Chem. Soc. 135, 5270-3.
4. Chakraborty, S. Liu, R. Hayouka, Z. Gellman. H.S. (2013). Studying the effect of cyclic versus acyclic nylon-3 polymers. ACS macro letter.

Conventional wisdom has always held that transition states are impossible to observe and characterize experimentally. With the exceptions of ultrafast spectroscopy and ab initio electronic
structure calculations, direct information about these critical points on potential energy surfaces has therefore been very limited. We have recently demonstrated for the first time that it is possible to
characterize a transition state by high resolution spectroscopic methods, using the cis-trans isomerization in the well-known A state of acetylene as a prototypical system. New spectroscopic patterns related to the properties of transition states will be discussed, in addition to the experimental and theoretical techniques employed to decipher the complex spectra and dynamics of isomerizing molecules.