Tuesday, January 23, 2018   |   through Tuesday, January 23, 2018   |   4pm   |   HSB, T-639   |   Speaker: Robert P. Dickson, MD   |   Host: Dr Pradeep Singh

In this seminar, I will discuss the microbial ecology of the human respiratory tract. I will share recent insights into the abundance, identity, origin, and viability of lung
bacteria in health, and will explore how critical illness radically alters the ecology of the lower respiratory tract. I will present experimental evidence supporting the
hypothesis that the microbiome plays a key role in the pathogenesis of sepsis and the acute respiratory distress syndrome (ARDS). Finally, I will share our group's recent
experience using real-time metagenomic sequencing to identify respiratory pathogens faster than culture-based clinical protocols.

Tuesday, January 30, 2018   |   through Tuesday, January 30, 2018   |   4pm   |   HSB, T-639   |   Speaker: Ned Ruby, Ph.D.   |   Host: Dr Carrie Harwood

‘If you build it, they will come’

The importance of surface structures in a beneficial colonization

Ned Ruby

University of Hawaii at Manoa

The initial encounter between a beneficial bacterium and its host is both a chemical and physical event, involving signal molecules and surface interactions. Discovering and understanding the cellular structures supporting this kind of communication, and the temporal pattern through which these events play out during the early stages of colonization, provides a window into the workings of coevolved adaptations between the two partners. One well understood initiation program is that unfolding during the first few hours of the interaction between the newly hatched juvenile squid Euprymna scolopes and its bioluminescent symbiont, Vibrio fischeri.  Here we discuss recent discoveries concerning the part played by several cellular structures of both the host and its bacterium. Specifically, the focus will be on (i) two classes of cilia involved in capturing and sorting the planktonic symbionts, (ii) host-induced modifications of the bacterium’s outer envelope as it senses and adjusts to the host tissue environment, and (iii) the role of the flagellar sheath in delivering symbiont-derived signal molecules that initiate tissue differentiation in the nascent host.  Together, these events define the trajectory of colonization, and provide clues to mechanisms of host interaction that have counterparts in other members of the genus Vibrio, and beyond.


Tuesday, February 13, 2018   |   through Tuesday, February 13, 2018   |   4pm   |   T-639   |   Speaker: Mirko Paiardini, PhD   |   Host: Dr Jim Mullins

This presentation will discuss state-of-the-art concepts and immune based strategies targeting HIV persistence developed over the past several years using the model of SIV infection in rhesus macaques (RMs). Collectively, these studies support a model in which among memory CD4+ T-cells, those expressing co-inhibitory receptors (Co-IRs) are enriched in latent HIV. Recent work identified PD-1+ follicular helper CD4+ T-cells as an important cellular compartment for viral persistence. We have described that CTLA-4+PD-1- memory CD4+ T-cells, which share phenotypic markers with regulatory T-cells and localize outside the B-cell follicle of the lymph nodes, are significantly enriched in SIV-DNA; contain robust levels of replication-competent virus; and significantly increase their contribution to the SIV reservoir with prolonged ART. Finally, we showed that Interleukin-21 administration in ART-treated, SIV-infected RMs reduces residual inflammation in blood and intestinal mucosa, which is in turn associated with diminished viral persistence during ART.

Tuesday, February 20, 2018   |   through Tuesday, February 20, 2018   |   4pm   |   HSB T-639   |   Speaker: Sebla B. Kutluay, Ph.D.   |   Host: Dr Jaisri Lingappa

Following their release from the host cell plasma membrane, HIV-1 particles undergo virion maturation during which viral ribonucleoprotein complexes condense inside a remodeled conical capsid shell. While virion maturation is thought to be largely driven by the proteolytic cleavage of the viral major structural protein, Gag, mutational studies of HIV-1 Integrase (IN) more than two decades ago implied its key role in this process. We have recently discovered that IN drives proper particle maturation by binding to the viral genomic RNA. In follow up biochemical and genetic studies in our lab,  we found that IN-RNA interactions are tightly linked to the multimeric state of IN. Using aberrant particles generated by manipulation of IN as a tool to gain a better understanding for early post-entry steps, we uncovered a role for the capsid lattice in protecting the viral genome and IN from degradation by the host cell machinery.  Together, our recent work has revealed a key role for IN in proper formation of the viral core and protection of the viral RNPs in target cells upon infection.