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cAMP dependent Protein kinase (PKA) plays a critical role in numerous neuronal functions including neuronal excitability, synaptic plasticity, learning and memory. Specificity in PKA signaling is achieved in part by the four functionally non-redundant regulatory (R) subunits. The inactive holoenzyme has a dimeric R subunit bound to two Catalytic (C) subunits. The full-length holoenzyme crystal structures allow me to understand how isoform-specific assembly can create distinct holoenzyme structures that each defines its allosteric regulation. High-resolution large-scale mosaic images provide global views of brain sections and allow identification of subcellular features. Analysis of multiple regions demonstrates that the R isoforms are concentrated within discrete regions and express unique and consistent patterns of subcellular localization. Using the miniSOG technique for correlating fluorescent microscopy with electron microscopy I find RIβ in the mitochondria within the cristae and the inner membrane, and in the nucleus, modifying the existing dogma of cAMP-PKA in the nucleus. Down-regulation of the nuclear RIβ, but not RIIβ, decreased L-LTP related signaling as reported by CREB phosphorylation in primary neuronal cultures, consistent with deficits observed in RIβ knockout mice. Furthermore, we show that a point mutation in the RIβ gene, that is associated with a neurodegenerative disease, abolishes dimerization while retaining robust interaction with the catalytic subunit. As a consequence, the interaction with an A-Kinase Anchoring Protein (AKAP) was also diminished. This mutation abolishes the AKAP-mediated targeting of RIβ holoenzymes to specific cellular compartments, which is consistent with an accumulation of RIβ in neuronal inclusions in patients carrying this mutation. These diverse interdisciplinary tools are defining PKA signaling as highly localized complexes that are targeted to specific sites in the cell in close to proximity to substrates and other signaling molecules where activity is then regulated by local levels of cAMP and calcium as well as kinases and phosphatases.

Topological Insulators (TIs) are a newly discovered class of materials in which symmetry-protected conducting modes exist on the surface of a bulk insulator. They hold promise for realizing a variety of fundamentally interesting and technologically relevant electronic phases, ranging from quantized magnetoelectric effects to device structures that support extremely high thermoelectric performance. Surprisingly, removing symmetries from these materials – including those that underlie their fundamental protection – has proven to be on the most incisive ways of examining TIs and reaching towards these exotic electronic behaviors. I will discuss our materials oriented approach to breaking symmetry in TIs and the new behavior is has uncovered with a focus on emergent quantum Hall phases.

Abstract:
Charge symmetry breaking (CSB) in the light hadronic spectrum,e.g. the neutron-proton mass difference, has been recently explained by LQCD-LQED calculations in terms of the u-d quark mass difference plus electromagnetic interactions among the u,d,s quarks. A similar level of understanding CSB is lacking for two-baryon configurations (e.g. pp, pn and nn, and more so for Lambda-p and Lambda-n). In nuclei, the CSB contribution of about 70 keV to the Coulomb-dominated 764 keV 3He-3H mass difference is accounted for by hadronic contributions. Given this background, the CSB implied by the Lambda separation energy difference 350+/-60 keV in the A = 4 mirror hypernuclei ground states, obtained by attaching a Lambda hyperon to the (3H, 3He) mirror nuclei, is LARGE. It has defied theoretical attempts to reproduce it in terms of CSB in hyperon masses and in hyperon-nucleon interactions, including one pion exchange arising from (Lambda Sigma0) mixing. In this talk I will review new calculations of CSB in the A = 4 Lambda hypernuclei, plus extensions to heavier mirror Lambda hypernuclei, using several strong-interaction (Lambda N Sigma N) coupling potential models, including a chiral EFT model in leading order. These calculations demonstrate for the first time that the observed CSB splitting of mirror levels in Lambda hypernuclei can be reproduced using realistic theoretical interaction models.

Tropical cyclones are generally thought of as being of too small scale to be simulated adequately in the global climate models in use for studies of global warming. But these models are gradually moving to higher resolution and are beginning to provide realistic simulations of the statistics of tropical cyclones. In addition to providing some information on how tropical cyclone statistics might change in the future, these models now provide a framework for studying how the climatology of tropical cyclones is controlled. I will describe a hierarchy of models with which we are beginning to address this issue.

Our body is colonized by trillions of microbes, known as the human microbiome, living with us in a complex ecological system. Those micro-organisms play a crucial role in determining our health and well-being, and there are ongoing efforts to develop tools and strategies to control these ecosystems.
In this talk I address a simple but fundamental question: are the microbial ecosystems in different people governed by the same host independent (i.e. “universal”) ecological principles? Answering this question determines the feasibility of general therapies and control strategies for the human microbiome. I will introduce our novel methodology that distinguishes between two scenarios: host-independent and host-specific underlying dynamics. This methodology has been applied to study different body sites across healthy subjects. We also analyzed the gut microbial dynamics of subjects with recurrent Clostridium difficile infection (rCDI) and the same set of subjects after fecal microbiota transplantation (FMT). The results can fundamentally improve our understanding of forces and processes shaping human microbial ecosystems, paving the way to design general microbiome-based therapies.