Issue 254
Our Phage Picks for March 2024!
We're starting off the year by trying a new format: Phage Picks — where we share the papers we keep bookmarked... and keep coming back to.
Community digest5updates8jobs2posts
Updates
Pherecydes has a new phage therapy patent. It covers new S. aureus phages and their manufacture and combination for use in phage therapy and as a companion diagnostic.
NIAID seeks applications from single institutions or consortia ready to generate, validate, and advance medical countermeasures against drug-resistant bacteria or fungi.
Nicholas Smith (University at Buffalo) and colleagues published a new paper exploring the pharmacodynamics of three unique Pseudomonas phages by simulating different dosing strategies (cocktails vs. single phage, bolus vs. prolonged dosing) using a hollow fibre infection model and mathematical modeling.
Ana Rita Costa (Delft University of Technology) and colleagues published a new paper showing that clinical P. aeruginosa strains accumulate phage defense systems (some have at least 19!), that many individual defense systems target specific phage genera, and that defense systems with complementary specificities co-occur in P. aeruginosa genomes.
Ritu Arora (University of Delhi) and colleagues isolated 100+ mycobacteriophages over the last two years, and here announce five genomes from different clusters, infecting M. tuberculosis and M. fortuitum.
Jobs
Postdoctoral position: Bacteriophage biology at CNRS in Lyon, France.
The project aims at deciphering if and how prophages mediate resistance against, and coevolve with, virulent phages in the opportunistic pathogen Pseudomonas aeruginosa. The candidate will join a newly created group at the Molecular Microbiology and Structural Biology (MMSB) unit (CNRS, Université de Lyon, France)
For further information: anne.chevallereau@cnrs.fr
UC San Diego is hiring a Staff Research Associate to design and construct jumbo phage genomes for new phage production, involving computational design, synthetic biology, and yeast genetics.
FDA (Silver Spring, Maryland) is offering a postbac fellowship to develop and characterize phage therapy for decolonizing Vancomycin-resistant Enterococci, focusing on overcoming bacterial resistance.
EPFL (Lausanne, Switzerland) is hiring a postdoc to explore phage-bacteria interactions within stream biofilms using microfluidic techniques.
University of Nottingham, UK, is offering a PhD Studentship to develop phage therapy strategies against C. difficile, involving synthetic biology, CRISPR/Cas genome editing, and microbiology.
Washington University (St. Louis, USA) is hiring a Research Technician II to support phage and bacterial host interaction studies, involving molecular biology, cell biology, and genomics.
The University of Pennsylvania is hiring a Research Specialist to lead a project on molecular interactions between bacteria and phage.
FAPESP, São Paulo, Brazil is hiring a postdoc to explore the applications of bactericidal type IV secretion systems, focusing on interspecies bacterial warfare and the development of new tools for targeting pathogens.
Community board
This week on PhageCast, the team talked to Paul Turner about how his lab is predicting the trade-offs of bacterial resistance to phage, to achieve killing by reversing the antibiotic resistance. They also covered how these findings are translated from in vitro to in vivo, and he also gave really inspiring advice for the people in the field.
The International Society of Microbiota will host their 11th Annual Meeting, Targeting Microbiota, on October 17-18 at the Corinthia Palace Malta, to explore the role of microbiota in health and disease, advancements in microbiome medicine, and the clinical applications of phage therapy, among other topics.
Hi everyone!
We thought we'd kick off the year with a new format.
We've been reading phage papers for years — and have amassed a trove of our favorites. These are papers we come back to: over and over and over. They make us think. Reflect. And get us excited to get back in the lab (or computer) again!
We call these Phage Picks, and we urge you to take a look. These are casual recommendations of papers — from colleague to colleague.
We hope these papers excite you as much as they excite us!
Rapid assessment of changes in phage bioactivity using dynamic light scattering
What is it about?
Tejas Dharmaraj (Stanford University) and colleagues show us how to use Dynamic Light Scattering (DLS) as a simple, fast way to measure phage stability. DLS is commonly used in physics to quickly measure particle size, and many university departments likely have one of these machines already (try asking around!). Instead of always needing to do plaque assays, we can use DLS to get a quick readout on whether a phage has degraded or aggregated in solution, or if it’s still stable (and thus active — crucially, this paper shows how DLS correlates nicely with plaque assay-derived titres, although one thing it can’t detect is UV-induced damage).
Why we’re excited about it:
Anything that cuts down on time spent doing endless titres is golden in my books. DLS is a reliable, cheap, fast, and non-destructive alternative to check for phage activity. By having this assay running in our phage labs, we can keep regular tabs on our phage preps and rapidly get a much better sense of phage stability across different conditions. Also, this paper gets into other super handy tools like a nice area-under-the-curve assay for quantifying how much a phage has degraded/aggregated in solution, as well as software to readily analyze the DLS data (called PhageELF). Overall this is an awesome tools paper that everyone in the phage field needs to read!
~ Jessica
Tejas Dharmaraj, Michael J Kratochvil, Julie D Pourtois, Qingquan Chen, Maryam Hajfathalian, Aviv Hargil, Yung-Hao Lin, Zoe Evans, Agnès Oromí-Bosch, Joel D Berry, Robert McBride, Naomi L Haddock, Derek R Holman, Jonas D van Belleghem, Tony H Chang, Jeremy J Barr, Rob Lavigne, Sarah C Heilshorn, Francis G Blankenberg, Paul L Bollyky, Rapid assessment of changes in phage bioactivity using dynamic light scattering, PNAS Nexus, Volume 2, Issue 12, December 2023, pgad406, https://doi.org/10.1093/pnasnexus/pgad406
Large language models improve annotation of prokaryotic viral proteins
What is it about?
In this paper, the authors documented how they used protein language models (PLMs) to annotate proteins, as opposed to traditional methods. The team trained existing PLMs with well-annotated databases like PHROGS — and found 29% more protein annotations — including finding new integrases and a capsid protein.
Why we’re excited about it:
Using a rough analogy, traditional annotation tools are like “spell checkers” while PLMs are like ChatGPT. While spell checkers are decent at identifying and correcting words and sentences, they’re fairly rigid. While they can infer “Mivi is a cat” is about a cat, they fall apart on sentences like “Mivi loves tuna and purrs when it rains.” Meanwhile, large language models like ChatGPT can infer these because they’ve “seen” relationships between “tuna” and “purr” with cats in their training data.
This is super exciting because these tools can find “synonymous annotations” that we previously missed. This could help us detect more integrases before taking a phage to therapy, help us clean up annotation databases, and potentially even lead to discovering new patterns that could open up new research areas. Excitingly all the code and data is also contained in the paper (as a Github repo), so anyone can go in and reproduce it (I haven’t done this myself yet.) ~ Jan
Flamholz, Z.N., Biller, S.J. & Kelly, L. Large language models improve annotation of prokaryotic viral proteins. Nat Microbiol 9, 537–549 (2024). https://doi.org/10.1038/s41564-023-01584-8
That's it, those are our favorite drops for this week! We'll experiment with bringing you a new bunch of fresh picks every month — of a mix of 80's, 90's and today!
Oh and if you have suggestions for new papers, or how we can improve the format, let us know (jan@phage.directory). Any feedback (nice or mean) will help us make Capsid more useful for you!
~ Jan & Jess
Jan Zheng, MHCI
I'm Jan, the other half of Phage Directory, and co-write Capsid & Tail.
Previously, I did data work at Phage Australia / Westmead Institute, where I built the biobank databases, data systems, and bioinformatics workflows for the clinical trial
I have a background in computer science and human-computer interaction, and I'm currently full-time at building the agentic layer for science at Nvidia.
Jessica Sacher, PhD
I'm a co-founder of Phage Directory and have a PhD in Microbiology from the University of Alberta (I studied Campylobacter phage biology). For Phage Directory, I help physicians find phages for their patients, and I'm always trying to find new ways to help the phage field grow (especially through connecting people and highlighting awesome stuff I see happening in the field).
I spent 2022-2024 as a postdoc in Jon Iredell's group at Westmead Institute for Medical Research in Sydney, Australia, helping get Phage Australia off the ground. I helped set up workflows for phage sourcing, biobanking, diagnostics, production, purification and QC of therapeutic phage batches, and helped build data collection systems to track everything we did. We treated more than a dozen patients in our first year, and I'm so proud of that!
As of 2024, I joined the Bollyky lab at Stanford University as a Staff Scientist, where I'm focused on phage engineering and delivery (to both microbial and human cells) and hydrogel-embedded phage cocktail development for wounds!