Integrated Calendar

Abstract:
Disulfide bonds are covalent cross-links that stabilize and regulate proteins. Disulfides are typically introduced into proteins as they fold in the endoplasmic reticulum (ER), and a great number of enzymes are present in the ER to help with this process. Despite the predominance of the ER as the site of disulfide cross-linking, an additional disulfide catalyst, called Quiescin Sulfhydryl Oxidase (QSOX), is found in the Golgi apparatus. We have investigated the function of QSOX in cultured cells and animals and have found that it participates in the formation of extracellular “smart fabrics” such as fibrous matrices and mucus. The structural and compositional complexity of these materials makes studying them on the biomolecular level a great challenge, but their enormous importance to cell and organismal biology inspire us to seek novel approaches.
Bio:
Deborah Fass received her scientific training at Harvard and MIT and came to Israel in 1998 to join the Department of Structural Biology. She has a background in molecular virology and protein folding. She became interested in disulfide bond formation by studying how virus envelope proteins manipulate endoplasmic reticulum chaperones to acquire “spring-loaded” conformations that prime them to penetrate new target cells. Over the past two decades, she has been continually surprised at how many interesting and unexpected biological processes are controlled by disulfide bond formation.

Tremendous progress has been achieved in the coherent control of single quantum states (single charges, phonons, photons, and spins). At the frontier of quantum information science are efforts to hybridize different quantum degrees of freedom. For example, by coupling a single photon to a single electron fundamental light-matter interactions may be examined at the single particle level to reveal exotic quantum effects, such as single atom lasing. Coherent coupling of spin and light, which has been the subject of many theoretical proposals over the past 20 years, could enable a quantum internet where highly coherent electron spins are used for quantum computing and single photons enable long-range spin-spin interactions. In this colloquium I will describe experiments where we couple a single spin in silicon to a single microwave frequency photon. The coupling mechanism is based on spin-charge hybridization in the presence of a large magnetic field gradient. Spin-photon coupling rates gs/2 > 10 MHz are achieved and vacuum Rabi splitting is observed in the cavity transmission, indicating single spin-photon strong coupling. These results open a direct path toward entangling single spins at a distance using microwave frequency photons.

Intracellular metabolites that give rise to quantifiable MR resonances are excellent structural probes for the intracellular space, and are oftentimes specific, or preferential enough to a certain cell type to provide information that is also cell-type specific. In the brain, N-acetylaspartate (NAA) and glutamate (Glu) are predominantly neuronal/axonal in nature, whereas soluble choline compounds (tCho), myo-inositol (mI) and glutamine (Gln) are predominantly glial. The diffusion properties of these metabolites, examined by diffusion weighted MR spectroscopy (DWS) exclusively reflect properties of the intracellular milieu, thus reflecting properties such as cytosolic viscosity, macromolecular crowding, tortuosity of the intracellular space, the integrity of the cytoskeleton and other intracellular structures, and in some cases – intracellular sub-compartmentation and exchange.

The presentation will introduce the basic methodological concepts of DWS and the particular challenges of acquiring robust DWS for accurate estimation of metabolite diffusion properties. Subsequently, the unique ability of DWS to characterize cell-type specific structural and physiological features will be demonstrated, followed by several applications of DWS to discern cell-type specific intracellular damage in disease, especially in multiple sclerosis (MS) and in neuropsychiatric systemic lupus erythematosus (NPSLE). Also discussed are the advantages and the challenges of performing DWS at ultrahigh field will follow, and the possibilities of combining DTI/DWI and DWS in a combined analysis framework aimed at better characterizing tissue microstructural properties in health and disease. The presentation will conclude with examples of the potential of DWS to monitor and quantify cellular energy metabolism, where enzymatic processes may affect the diffusion properties of metabolites involved in metabolism.

Acute myeloid leukemia (AML) is a devastating disease with less than 10% of elderly patients survive five years. While AML originates from stem cells which evolve over many years it presents acutely due to the expansion of more committed progenitors. Over the recent years we were able to identify the origins of AML relapse, and also to study AML years before it is diagnosed. We now can predict AML 6 years before diagnosis. Future studies will soon provide evidence whether early treatment will be beneficial.