Hi phage friends,
We’re at the end of the year again, and what a whirlwind of a year it’s been! These years are just whizzing by aren’t they? It still feels like yesterday when we were making new years resolutions for what we wanted to get done in 2022.
At the end of the year, we’ve always liked to spend the last issue of Capsid to reflect on the past year, to look at all progress we’ve made and all the cool stuff we’re proud of, and to highlight our amazing collaborators and volunteers!
Setting up phage therapy in Australia
By far the biggest thing we’ve done this year was move to Sydney to help set up the Phage Australia initiative.
Some of Jessica’s proudest achievements
Helped set up a phage therapy process pipeline & started treating patients!
This year I’m especially proud of helping get Phage Australia’s phage therapy pipeline off the ground! All of this work has been done alongside Stephanie Lynch, who you all know from Phage Directory — luckily for all of us, she is also a core driver of Phage Australia! Steph is the is the master of all things screening and biobanking, as well as making sure hospitals have the right paperwork in place to treat patients, among about a million other reasons this ship wouldn’t be sailing without her…
A few specifics I’m proud of:
- We established a system of phage biobanking, & got started banking (essentially re-isolating, titring, sequencing, labeling, & adding to a database) 300+ Iredell lab phages. We also began adding collaborators’ phages (thanks especially to Heejoon Myung, who sent us tons of phages!)
- We screened 47 patients’ isolates, found phages against 23 of them, & produced batches of 14 of them!
- We established a working pipeline for phage production, purification, and quality control (I blogged about each on Phage Australia’s blog, & each of these also appeared in C&T here, here & here).
- We created a set of four reports for local hospital drug/ethics committees to approve phages that go into patients, and gotten the first three sets of documents submitted and approved (this process was initiated after conversations with the TGA, Australia’s FDA, who asked us to help them regulate phage therapy — excited to keep workshopping these docs with them in the new year)
- We treated 3 patients at two hospitals with phages we made, purified and QC’d in-house (1 E. coli and 2 P. aeruginosa patients; each got 2-3 phages; each had multiple infecting strains; all three are doing well; first two are now culture-negative & feeling better)
- We shipped one of our first purified phages to 4 labs (in 4 states) around Australia and had everyone titre it, as an exercise in how shipping & different hands might affect phage titres (Steph wrote a blog post about it here)
- We created a system (mostly using Notion) to keep track of protocols, protocol templates, sample inventory, and patient cases (phage list, strain list, batch list, case list, etc)
Spoke about our phage therapy process and pipeline
- Bioprocessing Network (Sydney, Australia): I gave a talk on some of our challenges on the manufacturing side
- Australasian Virology Society (Gold Coast, Australia): I presented a poster & Steph gave a talk (which won an award for Best Talk in Clinical Virology!!)
- I gave a talk to AMMI Canada (Association of Medical Microbiology and Infectious Disease Canada) about our ‘Four Reports’ system for demonstrating phage safety, & how we might expand this to other countries ready to consider implementing it, like Canada
- Westmead Institute for Medical Research (Meet the Researcher) — where Jon Iredell and I did a brief Q&A for the public about Phage Australia and a bit about Phage Directory too
Some of Jan’s proudest achievements:
This year I’ve spent a lot of time brushing up on a lot of technical subjects, like handling bucket storage, edge workers, API-first development, and exploring database ideas like graph and event-driven databases and architectures like the triple entity-attribute-value model. I built a bunch of API-driven primitives (which I’ll be writing about and sharing next year!), and put up an awesome website and design for Phage Australia (phageaustralia.org) that runs on top of Notion for blog and text content, and aggregates across Google Sheets for the phage and bacterial data.
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Building our own “Phage therapy operating system on top of actual data and actual cases. This is something I’ve been very keen to do since we devised the concept a couple of years ago. Instead of building and design around others’ workflows, we’re now designing and building it around our own. As part of Atlas, we’ve been building a data aggregation system, designed a massive phage and bacteria biobanking schema, and an API to ingest lots of data (from CSVs to plaque assay images to genomics files), and lots of other primitives. Don’t worry — we’re still hoping for a public release at some point!
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Getting a data collection system put in place: From computation (DUG) to setting up a shared data storage system (Cloudflare R2) to using Google Sheets to coordinate and aggregate data across labs and efforts — pieces are coming together
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Designed and built a “mostly dynamic” patient data collection system on top of REDCap to its limits, by programmatically generating REDCap using a new programming language called CUE
All in all, we’ve been productive, but have also enjoyed the heck out of Sydney! We’ve only had “a few” run-ins with Huntsman spiders, and still haven’t seen any wild drop bears or kangas, but overall we’ve loved our time here so far. We might also have picked up some slang along the way…
Over 200 issues of Capsid & Tail!
It’s hard to believe we’ve published more than 200 issues of Capsid & Tail (including 47 this year)! This year’s issues have been our strongest ever. It’s been really exciting to share more our process of building up a scalable phage therapy treatment pipeline, both from a wet lab and dry lab perspective.
This year has been brimming with great posts, and we had trouble choosing our absolute favorite ones (of course, we might be biased, since we wrote so many ourselves!).
Some of our favourite guest-authored posts (22/47 articles this year were guest-authored!!):
Jessica’s favourite posts to write
These were my favourites to write because they marked my first attempt at actually writing about my personal experiences (and decision making processes) in the lab. It was much scarier than recapping a webinar or summarizing someone else’s work… but these posts garnered WAY more discussions and feedback and emails, including new ideas and suggestions for collaborations! So I want to do more of these next year for sure!
Jan’s favorite posts to write
Contribute a post to Capsid & Tail in 2023!
We would absolutely love more technical, nitty gritty posts on setting up the wet lab and dry lab processes for phage therapy next year. If you’re up for sharing some of your insights, don’t be afraid to write something for Capsid!
It’s still hard to believe, but every week, we have around ~700 phage enthusiasts read Capsid & Tail!
Oh, and Phage Directory is going strong!
Phage Alerts
We’ve handled a total of 44 Phage Alerts since we started, with 11 alerts sent this year.
Top five organisms phages are requested for (# alerts sent out)
- P. aeruginosa (5)
- E. coli (4)
- Mycobacterium avium (3)
- Klebsiella pneumoniae (3)
- Burkholderia cepacia (3)
For alerts we have sent out, 82% have led to at least one lab responding and offering phage screening (between 1- 20 responding labs per request)
8/44 (18%) had zero responding labs – this is the best proxy we have right now for hard-to-find phages, but of course lack of responders could be influenced by other things like timing of the alert
Organisms responsible for ‘zero response’ alerts:
- Helicobacter pylori, Mycobacterium abscessus (2022)
- Mycobacterium avium (2022)
- Propionibacterium avidum (2020)
- Streptococcus anginosus (2020)
- Mycoplasma genitalium (2019)
- Staphylococcus epidermidis (2018)
- Burkholderia cepacia (2017)
Organisms responsible for low responses (0-3 responses):
- Organisms span 23 species
- Mycobacterium (abscessus, avium, kansasii, genitalium) - 7 alerts
- Burkholderia (gladioli, cepacia, dolosa) - 5 alerts
Outside of that, we have gotten our most desperate requests from patients for Mycoplasma and Borrelia, but these essentially never have a doctor on board so we don’t send alerts.
Of note, for Mycobacterium we tend to send people directly to Graham Hatfull instead of doing an alert; this was a choice we made a few years back. So our Mycobacterium numbers would be underrepresented.
Community-building & phage data systems
- We’re proud to have successfully run the iVoM series and built a lot of the underlying poster and abstract submission systems for VoM. We’re also glad that we’ve taken a break from running Zoominars (so exhausting…), but we do really miss connecting with the community in that way… (We’re also sad we couldn’t make it out to VoM Portugal this year!)
- The Phage Directory back-end system has gone through a massive rehaul. Much of it’s not user-facing, but we now have a much more robust API-first system in the back, which means we’ll finally get to do more Phage Directory experiments next year!
- We’ve experimented with automating the Phage Directory registration system, but know a lot more can be done, and we’re doing those things next year.
- Instill is being rethought from ground up and ready to be launched very soon… and this time it’ll be integrated closely with Phage Directory!
Our volunteers make everything possible!
We wouldn’t be here without our army of the best volunteers! Many thanks go out to Atif Khan, Stephanie Lynch, Jessica Neubauer, Madhav Madurantakam Royam, Sayde Perry, Kyle Jackson, Katharine Muscat, and many many more! They’ve been incredible, from helping us to find job openings and news to contributing articles to Capsid & Tail to helping us tweet news to keeping our Slack fun. Here’s a breakdown of how our volunteers have helped us this year!
Also, many thanks to everyone who’s asked and answered questions on Phage Slack!
Thank you sponsors and partners!
Thank you to your continued support throughout the years, JAFRAL, Cellexus, Kisaco Research: Phage Futures, and PHAGE Journal!
Also a huge shout out to VoM and ISVM. We’re really sad we couldn’t make it out out to VoM Portugal this year, but we had a lot of fun hosting iVoM and building the Abstract Portal!
Thank you to Phages for Global Health for your continued support.
A HUGE thank you to Grant for the Web for supporting Instill and our experimental ideas in push forward community-building and publishing.
Last but not least, thank you to Phage Australia, particularly Jon Iredell and Ruby Lin, for giving us a chance to build out the phage therapy pipeline of our dreams! And lastly thanks to all our amazing colleagues here at WIMR in Sydney, such as Stephanie Lynch, Ali Khalid, Nouri Ben Zakour, and many more.
What’s in store for 2023?
We’ve made the great leap to Australia, set up a phage therapy pipeline, but we’re still just getting started! We have lots of ideas for next year, including scaling up our phage therapy process, rolling out our phage data collection system, and maybe even experimenting with new Capsid formats and turning Phage Directory into something more community oriented… but we’ll get more into all of that in January. Between now and then, let’s everyone get some time off with friends and family!
Cheers, and see you in the new year!
— Jess & Jan <>={
Many thanks to Atif Khan for finding this week’s phage news, jobs and community posts, and Jessica Neubauer for tweeting & LinkedIn-ing them out!
