March Madness is Upon Us!

Despite Dr. Heisler’s attempts to use the real March Madness tournament brackets (NCAA WRESTLING) we are going to having a lab competition!

The winner gets to pick a baked good they want Dr. Heisler (David’s wife) to bake for next month’s lab meeting on April 16th. Additionally, and probably more important than PCR superiority, you get BRAGGING rights for a whole year!

Points will be awarded for each pick as follows:
+2 for round 1
+4 for round 2
+8 for Sweet 16
+16 for Elite 8
+32 for Final 4
+64 for Championship

Check back regularly for updated rankings and to see who the winner will be!

Latest Pre-Print From Dr. Heisler’s Postdoc is online

Released today on bioRxiv, the Alto and Gammon labs identify previous unknown host factors that restrict viral replication during cellular infections. Led by graduate student Aaron Embry, this study used a library of bacterial effector protein genes, which Dr. Heisler generated, to screen for proteins that suppressed host immune factors and allowed an otherwise restricted virus to replicate in cells. One effector protein, called Ceg10, that rescued all of the viruses tested, was shown by Dr. Heisler to have a Cys-His-Asp catalytic active site and, using limited proteolysis and X-ray crystallography, a high resolution structure of the core domain of the protein was solved. Additional work remains to be done to determine exactly what Ceg10 does and what its host target(s) is, but a lot of promising work is underway to figure this out!

Abstract:

Arboviruses are a diverse group of insect-transmitted pathogens that pose global public health challenges. Identifying evolutionarily conserved host factors that combat arbovirus replication in disparate eukaryotic hosts is important as they may tip the balance between productive and abortive viral replication, and thus determine virus host range. Here, we exploit naturally abortive arbovirus infections that we identified in lepidopteran cells and use bacterial effector proteins to uncover host factors restricting arbovirus replication. Bacterial effectors are proteins secreted by pathogenic bacteria into eukaryotic hosts cells that can inhibit antimicrobial defenses. Since bacteria and viruses can encounter common host defenses, we hypothesized that some bacterial effectors may inhibit host factors that restrict arbovirus replication in lepidopteran cells. Thus, we used bacterial effectors as molecular tools to identify host factors that restrict four distinct arboviruses in lepidopteran cells. By screening 210 effectors encoded by seven different bacterial pathogens, we identify six effectors that individually rescue the replication of all four arboviruses. We show that these effectors encode diverse enzymatic activities that are required to break arbovirus restriction. We further characterize Shigella flexneri-encoded IpaH4 as an E3 ubiquitin ligase that directly ubiquitinates two evolutionarily conserved proteins, SHOC2 and PSMC1, promoting their degradation in insect and human cells. We show that depletion of either SHOC2 or PSMC1 in insect or human cells promotes arbovirus replication, indicating that these are ancient virus restriction factors conserved across invertebrate and vertebrate hosts. Collectively, our study reveals a novel pathogen-guided approach to identify conserved antimicrobial machinery, new effector functions, and conserved roles for SHOC2 and PSMC1 in virus restriction.

To read more, visit https://www.biorxiv.org/content/10.1101/2024.01.29.577891v1

Welcome Cate!

The Heisler lab is excited to welcome Cate to this lab this spring. Cate is a passionate biology student who is eager to gain hands-on research experience. Cate will be focused on understanding how membrane cholesterol levels regulate bacterial pathogenesis of a variety of human pathogens.

Welcome Declan!

A big welcome is needed to our newest lab member, Declan. He is an freshman Biochemistry major with a personal interest in science and law and one day hopes to pursue both a PhD and JD to do patent law. While he will not have a defined project this semester, he will be exposed to everything the Heisler lab can do and we look forward to seeing evolve over the next three years.

First grant FUNDED!

The Heisler lab is excited to say that our inaugural grant, a Duquesne seed grant investigating dreaded diseases, has been funded! This will us to explore the role of proteins in the intracellular lifecycle of Listeria and establish a novel platform for exploring protein-protein interactions here at Duquesne.