Mol Bio Colloquium

Mol Bio Graduate Colloquium
Date
Oct 18, 2022, 1:30 pmOct 21, 2022, 4:00 pm
Location
Thomas Laboratory, 003
Audience
Free and open to the university community and the public.

Speakers

Amy Nelson
Graduate Student
Ploss Lab
Grace Beggs
Postdoctoral Fellow
Bassler Lab

Details

Event Description

GRAD STUDENT

 

AMY NELSON

Ploss Lab

 

Delineating mechanisms of Usutu virus pathogenesis in vivo

 

Arthropod-borne flaviviruses, such as Dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV) and yellow fever virus (YFV), are significant global health and economic burdens, which cause more than 400 million infections annually.Flaviviruses comprise a genus of enveloped, positive, single-stranded RNA viruses which are transmitted between susceptible hosts by arthropod vectors, such as ticks and mosquitoes. While some flaviviruses such as DENV and YFV have been intensively studied, there are few approved treatments and prophylactic vaccines. Additionally, there is a portion of understudied, yet closely related viruses which cause disease in animals and have the ability to emerge in human populations. One such example is Usutu virus (USUV) - first isolated in 1959 in eSwatini (Africa) – which is part of the Japanese encephalitis virus serocomplex and is closely related to WNV. Transmitted by mosquitoes, USUV has been confirmed to infect a wide range of animal hosts, including humans, but is mainly known for causing astounding lethality in wild bird species in European countries. While symptomatic cases in humans are currently limited to immunocompromised individuals, there is the potential for new strains to emerge with increased virulence through zoonotic transmission. Currently, USUV is poorly characterized and gaining insight into how this virus establishes infection would fill a major gap in knowledge. Therefore, I have constructed genetically defined infectious clones of USUV. My preliminary data demonstrate that while B, T, and natural killer (NK) cells are dispensable for controlling USUV infection in vivo, type I and III interferon-mediated antiviral defenses, particularly in the hematopoietic compartment, are essential for organism survival. Fatal disease in mice is associated with systemic viral spread, dysregulation of proinflammatory cytokines and pronounced splenic and hepatic histopathology. Building on these exciting preliminary data, I aim to define the mechanisms by which USUV establishes infection and – using genetic reporters – track the infection dynamics in vivo. I further aim to determine transcriptomic signatures of infection across relevant (mammalian vs. avian vs. insect) host species. Collectively, results from my work will shed light on how USUV hijacks host immune signaling to maneuver through susceptible landscapes and promote systemic infection.

 

 

 

 

 

 

 

 

 

POSTDOC

 

GRACE BEGGS

Bassler Lab

 

Inter-domain chemical communication between Vibrio cholerae and phage VP882

 

Bacteria are bombarded by infecting viruses, called phages, in natural habitats. Upon infection of a host bacterium, temperate phages must undertake one of two lifestyles: lysogeny or lysis. During lysogeny, the phage remains in the host and is passed down to offspring. When the phage chooses the lytic program, it replicates, kills the host, and spreads to new cells. Phages have been thought to transition between lysogeny and lysis exclusively in response to host stress and DNA damage. New research has upended this dogma by revealing that phages can monitor host sensory cues and exploit the information they garner to drive lysogeny-lysis lifestyle transitions. I will use a combination of genetic, biochemical, and structural approaches to explore mechanisms underlying chemical communication between vibriophage VP882 and its host, the global pathogen Vibrio cholerae. I am using biochemical methods to characterize interactions between two key signaling components in the quorum-sensing-induced phage lysis pathway. Additionally, I aim to solve the structures of these same signaling components, individually and in complex, enabling atomic-level-resolution understanding of the interactions required for the phage to undergo lifestyle transitions.

 

 

Sponsor
Department of Molecular Biology
Event Category
Graduate Student Colloquium