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An interesting paradox exists in the lung: a stable lipid interface must be maintained while individual lipids are rapidly exchanged and actively sorted. Surfactant protein B, SP-B, is critical to lung function, particularly for trafficking of lipids within pulmonary surfactant and altering lipid properties at the air-water interface. The N- and C-terminal segments of SP-B and synthetic analogs retain many of the properties of full-length SP-B and have proven suc¬cessful in treat¬ing respiratory distress. We are developing and applying ssNMR and EPR techniques to study the interplay between peptide partitioning, lipid dynamics, pep¬tide secondary structure and dynamics, lipid polymorphisms, and temperature, pro¬viding important in¬sights into lung sur¬factant function and more generally the enthalpic and entropic con¬tribu¬tions underlying amphipathic peptides interactions with and influence on phos¬pholipid assemblies. Our method¬ologies and samples pre¬sent unique challenges due to the thermal properities of the samples and the need for strong RF excitation fields. Using static and MAS ssNMR experi¬ments coupled with EPR measurements and molecular dynamics simulations, we are de¬veloping a molecular level understanding of the varied structure and function of pulmonary surfactant peptides and their effects on lipid dynamics and speci¬ation. Our results highlight lipid-dependent structural plasticity and unusual amphipathic helical secondary struc-ture may be important to surfactant peptide functions. While both the C-terminal and N-terminal segments of SP-B are amphipathic helices, each displays unique properties which are complementary, explaining the success of chimeric constructs of these peptides in treating respiratory distress. Based on our studies, an understanding of the varying roles of the lung surfactant peptides is emerging.

The Japanese Hayabusa spacecraft returned to Earth on 13 June 2010 carrying within it a precious but invisible cargo - 1534 particles of dust from the surface of the asteroid Itokawa, which the spacecraft visited in 2005. These particles, up to 180 micrometer in size, are the first material ever fetched from an asteroid and returned to Earth for laboratory analysis. In the 26 August 2011 Science, six Reports, plus related news and commentary, discuss the mineralogy, petrography, chemistry, and noble gas and oxygen-isotope compositions of the Itokawa particles, which provide insights into the evolution of the solar system.

Cells transduce information across their plasma membrane via engagement of surface receptors and the subsequent recruitment of intracellular proteins to these receptors. Such receptor-regulated cellular signaling often results in the formation of transient, heterogeneous protein complexes and macro-molecular clusters that serve to amplify, relay and regulate the incoming signals. Important examples include signaling complexes downstream of receptor tyrosine kinases (RTKs), immune receptors and G protein-coupled receptors (GPCRs). Although these signaling structures play a crucial role in health and disease, including immune activation, cancer, and HIV infection, the detailed biophysical mechanisms by which they assemble and serve to activate cells remain poorly understood due to shortcomings in current research techniques.
We have developed and applied two-color photoactivated localization microscopy (PALM) to study the organization, structure and function of signaling complexes in the activation of immune (T) cells, at the single molecule level. Using this method, individual molecules can be identified and localized with resolution down to ~20nm. Second-order and clustering statistics were applied to resolve size-distributions of signaling complexes and molecular interactions at the plasma membrane of the cells. Our results show that nanoclusters, signaling complexes as small as dimers and trimers, govern the earliest events of T cell activation through dynamic interactions. Importantly, we show that these signaling complexes assume, in several ways, novel patterns of nanoscale organization that are crucial for cell activation. Taking a multidisciplinary approach, including the use of genetic mutagenesis, targeted drugs, statistical analysis and Monte-Carlo simulations, we could trace mechanisms that govern the formation of these patterns. Such mechanisms include combinations of dynamic protein-protein and protein-lipid interactions, hop-diffusion, confinement and patterning by the cell cytoskeleton and plasma membrane. These results extend our understanding of the mechanism of immune cell activation, findings also relevant to other receptor systems. I will further discuss novel research techniques that we have developed to better study critical signaling pathways in live interacting cells and in molecular detail.