Bryan Bryson

Two pieces of fun news: 1. We've launched a new website for our lab: www.brysonlab.org 2. With some new funding, we are recruiting for new postdocs and graduate students. The projects build upon our previous studies of antigen presentation and phagosome biology and go into new exciting dimensions!

Happy to share our newest preprint on antigen presentation of Mtb-derived peptides on MHC-I: www.biorxiv.org/cgi/content/... This is a follow up to our previous paper where we applied immunopeptidomics to understand MHC-I presentation by Mtb-infected cells: elifesciences.org/articles/84070

We're excited! This study supports the concept that there are multiple ways to transfer proteins from the phagosome to the cytosol, and that Mtb specifically takes advantage of this.

Happy to share our newest preprint on antigen presentation of Mtb-derived peptides on MHC-I: www.biorxiv.org/cgi/content/... This is a follow up to our previous paper where we applied immunopeptidomics to understand MHC-I presentation by Mtb-infected cells: elifesciences.org/articles/84070

So, we were stuck. Our data point to a role for ESX-1 in presentation but was it the secretion system or some other response that is downstream of ESX-1? So we did 2 experiments 1. We did discovery MS with macrophages infected with an ESX-1 mutant and asked if we could see Mtb-derived peptides. No!

Happy to share our newest preprint on antigen presentation of Mtb-derived peptides on MHC-I: www.biorxiv.org/cgi/content/... This is a follow up to our previous paper where we applied immunopeptidomics to understand MHC-I presentation by Mtb-infected cells: elifesciences.org/articles/84070

OK, so ESX-1 controls galectin recruitment to the phagosome. Can we figure out a way to restore galectin positivity to the phagosome of an ESX-1 mutant? Yes, we used some previously identified small molecules and restored galectin positivity, but it did not rescue presentation.

Happy to share our newest preprint on antigen presentation of Mtb-derived peptides on MHC-I: www.biorxiv.org/cgi/content/... This is a follow up to our previous paper where we applied immunopeptidomics to understand MHC-I presentation by Mtb-infected cells: elifesciences.org/articles/84070

ESX-1 activity controls a lot in phagocytes, and we had previously demonstrated that the loss of presentation we saw was independent of interferon production. We still had a lot left to explore, and this preprint does just that.

Happy to share our newest preprint on antigen presentation of Mtb-derived peptides on MHC-I: www.biorxiv.org/cgi/content/... This is a follow up to our previous paper where we applied immunopeptidomics to understand MHC-I presentation by Mtb-infected cells: elifesciences.org/articles/84070

Excited to share our lab's newest preprint (strap in if you're excited about metabolism, species differences, or Mtb gene expression): www.biorxiv.org/content/10.1...

We think this work is important because: 1. It helps us think about species differences in new ways 2. It highlights a metabolic gate in Mtb-host interactions 3. It may help resolve long-standing challenges in translating concepts from mouse studies to humans

Excited to share our lab's newest preprint (strap in if you're excited about metabolism, species differences, or Mtb gene expression): www.biorxiv.org/content/10.1...

So we took a step back and realized that in our hands human macrophages have more lipid droplets (LDs) at baseline than murine macrophages, so we tested the hypothesis that human LDs regulated the ability of Mtb to acquire and store lipids. Inhibition of host TAG synthesis did the trick (partially)!

Excited to share our lab's newest preprint (strap in if you're excited about metabolism, species differences, or Mtb gene expression): www.biorxiv.org/content/10.1...

Many of these Mtb genes were associated with lipid metabolism, so we orthogonally validated these observations by tracking Mtb acquisition and storage of lipids using established techniques and found that Mtb readily forms intracellular lipid inclusions in mouse but not human macrophages

Excited to share our lab's newest preprint (strap in if you're excited about metabolism, species differences, or Mtb gene expression): www.biorxiv.org/content/10.1...

We often use mouse and human macrophages interchangeably to study Mtb-host interactions, but an open question in the field is how (if at all) different species impose unique stresses on intracellular Mtb

Excited to share our newest manuscript on antigen discovery and vaccine design for tuberculosis lead by Owen Leddy (everyone hiring new faculty in a few years, remember this name!) www.science.org/doi/10.1126/... #TBsky

We're super excited! These are needle in the haystack measurements out of the BL3 that Owen executed beautifully. These studies also provide us a path to antigen discovery and vaccine optimization in human cells. And it's generalizable -- we can definitely extend to other pathogens!

Excited to share our newest manuscript on antigen discovery and vaccine design for tuberculosis lead by Owen Leddy (everyone hiring new faculty in a few years, remember this name!) www.science.org/doi/10.1126/... #TBsky

Here, we apply immunopeptidomics in primary human phagocytes to identify Mtb peptides presented by infected cells on MHC-II and then optimize mRNA vaccines encoding these antigens.

Newest paper from the lab out today (doi.org/10.1084/jem....)! Here, we describe PathMHC, a novel MS-based approach to identify rare pathogen-derived peptides on MHC-I and MHC-II. We apply this to a range of pathogens Mtb, SARS-CoV-2, and Listeria.

Importantly, for Mtb, the results are consistent with our previous study (doi.org/10.7554/eLif...) where we showed that Mtb-derived peptides on MHC-I are enriched for type VII secretion system substrates underscoring our enthusiasm for including these antigens in TB vaccines.