Tag: Phage

Phase Genomics Announces Funding to Accelerate Discovery of New Lysin-Based Precision Antimicrobials

Posted on March 5, 2024 by Benjamin Mitchell - Uncategorized

SEATTLE (March, 4, 2024) – Phase Genomics, Inc., a leading innovator at the forefront of genomics technology development, today announced $1.5MM in new funding from the Bill & Melinda Gates Foundation to fuel a new antimicrobial discovery platform. Leveraging the power of lysins, phage-derived proteins that selectively kill specific bacteria and archaea, the program aims to address two immediate threats that will shape the next century: a growing global antibiotic resistance crisis and the challenge of reducing global greenhouse gas emissions. The foundation of this effort rests on Phase Genomics’ proprietary global phage atlas, developed with support from the Gates Foundation. Under this project, Phase Genomics will deploy its platform to develop antimicrobial agents that bypass resistance against Campylobacter infections and methanogenic archaea in ruminants that drive global methane emissions.

“Our work at the frontier of microbiome research has unlocked a wealth of new insights on phages, the viruses that infect bacteria. Now, with support from the Gates Foundation, we’re harnessing our global phage database with the goal of improving human and environmental health and providing a critical alternative to traditional antibiotics,” said Ivan Liachko, PhD, founder and CEO of Phase Genomics. “The need for breakthrough therapeutics to combat the growing AMR crisis is urgent. We’ve built the right technology to identify and engineer lysin candidates primed to combat microbes both in environmental settings as well as emerging AMR biothreats and help overcome the industry-wide inertia facing novel antibiotic development.”

Derived from bacteriophage (or simply, phage) genomes, lysins are highly specific lytic proteins that kill bacteria by dismantling the cell wall structure, sparing off-target healthy microbes that are often collateral damage in traditional, systemic antibiotic treatment. Lysin-based antibiotics are well-suited for rapid, scalable biomanufacturing and deployment. Targeted bacteria are also much less likely to develop resistance to lysins than both traditional antibiotics and intact phages, providing a sustainable and durable framework to counter the accelerating antibiotic resistance threat.

The new platform will build on data from Phase Genomics’ bacteriophage discovery engine which holds one of the world’s largest and most comprehensive collections of phage-microbe interactions containing hundreds of thousands of new host-resolved phage genomes. This continuously-growing phage interactome atlas is primed for the rapid discovery of wide-ranging classes of antimicrobial lysins derived from phages. The platform is superior to other approaches in both scale and accuracy, simultaneously resolving both microbial targets and the phages that infect them, with each pair containing a potential target-specific lysin candidate. Phase Genomics’ ProxiMeta™-powered phage atlas forms a deep well of target bacterial pathogens and new candidate biologics to tackle emerging drug-resistant pathogens and environmental biothreats.

This year-long project also marks a first-of-its-kind collaboration between Phase Genomics and Seattle-based Lumen Bioscience, who will assess lysin bioactivity in their robust and scalable microbial expression system.

Follow Phase Genomics on X and LinkedIn for the latest news and information.

About Phase Genomics

Phase Genomics applies proprietary proximity ligation technology to enable chromosome-scale genome assembly, microbiome discovery, as well as analysis of genomic variation and genome architecture. In addition to a comprehensive portfolio of laboratory and computational services and products, including kits for plants, animals, microbes, and human samples, they also offer an industry-leading genome and metagenome assembly and analysis software.

Based in Seattle, WA, the company was founded in 2015 by a team of genome scientists, software engineers, and entrepreneurs. The company’s mission is to empower scientists with genomic tools that accelerate breakthrough discoveries.

Contact

Eric Schudiske

eric@s2spr.com

Bacterial pathogens have their own nemesis, and mimicking it can help solve the global AMR crisis

Posted on March 5, 2024 by Benjamin Mitchell - ProxiMeta

image of the globe surrounded by images of plants and viruses

Decades of antibiotic use – and abuse – are triggering a global rise in antibiotic resistance and limiting the usefulness of these life-saving drugs. In a nod to the adage, “The enemy of my enemy is my friend,” a solution may lie with bacteria’s oldest adversary: phages, the viruses that prey upon them. Our team at Phase Genomics is harnessing groundbreaking new metagenomic data and AI to tap into the evolutionary innovations of phages – and to eradicate dangerous microbial pathogens with surgical precision.

The need could not be greater. Fewer new antibiotics are hitting the market. The UN estimates that by 2050, worldwide deaths from antibiotic-resistant “superbugs” will overtake deaths from cancer. Early 20th century scientists explored deploying phages to cure bacterial infections, an idea that has been recently resurrected. Phages are a staggeringly diverse class of bacteria-killers. By one estimate there are 10³¹ of them on this planet right now, vastly more than all living organisms combined. But using phages to cure infections has its own drawbacks: Mass production is difficult since phages only grow in bacteria, which can be difficult to culture, and it turns out bacteria have a barrage of defenses against intact viruses, imparting resistance against them.

While phages present one opportunity to help us stave off a return to the pre-penicillin past, we can also use their anti-bacterial weapons to launch a new arsenal rooted in synthetic biology. Phages produce proteins called lysins to destroy their hosts’ cell walls. These proteins have evolved over millennia to specifically target the phages’ hosts. They can be purified and used as precision antimicrobials, molecules that specifically kill the target bacteria without the collateral damage and resistance brought about by traditional wide-spectrum antibiotics.

Our team has used our unique genome sequencing technology to build the world’s largest catalog of the genomes of phages and the microbes that they attack – including the sequences of lysin proteins that they make. We’re harnessing this catalog to design, synthesize, and perfect lysin-based therapeutics that can attack bacterial pathogens safely, effectively, and with a surgical precision that today’s antibiotics lack.

Lysins hold tremendous advantages over traditional antibiotics. Antibiotics take out swathes of bacteria in our microbiomes that are essential for good health, leaving us more vulnerable to future infections – like the dreaded C. difficile – as well as to immune dysregulation. Yet most lysins target only the phage’s host species and its close relatives. And though antibiotic resistance spreads rapidly via plasmids, bacteria struggle to evolve resistance to exogenously introduced lysins.

Our collective knowledge of lysins to date comes largely from isolated experiments on phages or small-scale genomic studies. To deploy lysins as a life-saving solution, we need detailed knowledge of the intricate and intimate interactions between phages and bacteria. Phase Genomics has led this effort by building a vast catalog containing hundreds of thousands of phage genomes from different microbial environments. Our proprietary ProxiMeta technology employed for these experiments preserves unique information about essential ecological interactions in these microbiomes, including the host bacterial species that specific phages target. Thanks to this large and growing catalog of phage-microbe interactions, for many pathogenic bacteria, we can find specific lysins that could turn its cell walls into Swiss cheese.

We are using this foundational knowledge to build the first foundry for lysins. With support from the Bill and Melinda Gates Foundation, Phase Genomics is collaborating with Lumen Bioscience to design, grow, and purify lysins identified by our catalog. This proving ground will serve as the foundation for a future pipeline for lysin design – augmented by machine learning to hone target specificity, perfect performance and even create entirely new lysins with a desired target specificity. To make a custom-designed lysin against almost any bacteria, we would need to find a phage – and its lysin – that attacks it. This approach to lysin research and discovery has applications even beyond medicine, such as critically needed environmental remediation.

Our goal to develop therapeutic lysins would upend the existing paradigm for treating bacterial infections. Today, medical professionals have a shrinking pool of imperfect antibiotics that cut a swathe through our microbiomes to take out the bacterial bad guys. With lysins on the shelf as an option, we would be taking away this machete, and replacing it with a scalpel.

Bacteria Breakthroughs: Insiders’ Reflections on Commercializing Discoveries in the Phage Industry

Posted on November 14, 2022 by Benjamin Mitchell - Uncategorized

During this Fall’s Genome Startup Day event, we welcomed researchers and entrepreneurs that have taken the plunge into commercializing their phage discoveries. John Eisen, PhD, UC Davis professor and renowned genomics and microbiology researcher, spoke with Ivan Liachko, PhD, Founder and CEO for Phase Genomics, for a candid and lively fireside chat on the current state of phage research and innovation followed by a panel discussion with startup founders Jessica Sacher, PhD, of Phage Directory, Nathan Brown, PhD, of Parallel Health and Minmin (Mimi) Yen, PhD, of PhagePro.

In the opening moments of the Fireside Chat, Dr. Eisen regaled us with the origin of his fascination with microbes. Converting from an East Asian Studies major to a Biology major at Harvard College, Dr. Eisen was initially interested in birds, butterflies, and plants. However, an opportunity at a faculty member’s lab shifted his focus to the microbiome. Eisen began researching the bacteria residing in tubeworms, an ocean-dwelling species with no mouth or digestive system.

“It was just so weird, so unusual. Ever since then, I’ve been working on microbes”

This experience launched Eisen’s career into the strange and mysterious world of microbes. His research has since expanded to include microscopic creatures from the space station, depths of the ocean, Antarctica, and more recently, cat butts. While a seemingly peculiar topic of research, performing sequencing on felines is not a rare occurrence in the genomics community. Host, Dr. Ivan Liachko, notes projects such as Kitty Biome and Phase Genomics’ own Meowcrobiome, which also caught traction in earlier years.

Looking forward, our fireside chat speakers revealed their expectations for the rapidly-blooming phage industry. “People are finally getting a handle on the functional contributions of some of these microbes,” Eisen shared. Thus, doors are being opened to (legitimately) commercializing their unique properties. “I’m not sure the overselling is going down, but the legit stuff is going up,” Eisen concluded (referring to his Overselling the Microbiome Award, which brings to light companies that were over-ambitious in bringing microbiome products to the market).

Finishing their discussion, Liachko and Eisen focused on the role of startups in the phage industry. Eisen advocates for the flexibility of academic and industry careers, not seeing their differences as a barrier, but as a landscape in which one can pursue numerous options by following their own creativity and curiosity. Liachko voiced several anxieties early founders, specifically those leaving student and postdoc positions, may have when making the jump to industry. The fear of entering the unknown, the struggle to find mentors, and how to set oneself up for success in the biotech industry–all with which our panelists had ample experience and advice to give.

Opening the panel, moderator Juliana LeMieux asked the startup founders how they were able to take a scientific discovery and transition it into a business model. With a range of phage-related companies represented at the (virtual) table, the panelists described their challenges, surprises, and successes in entering the business realm.

Three Considerations for Early Founders

Here are the top three take-aways for early founders from this event’s panel discussion:

1. “Don’t be afraid to try and don’t be afraid of the rejection” -Dr. Minmin Yen

Dr. Yen, driven by her enthusiasm for phage research, started PhagePro, an early-stage biotechnology therapeutics company offering bacteriophage-based products to target bacteria and prevent infections in vulnerable communities. She discussed challenges she faced in convincing regulatory agencies and stakeholders to contribute resources to the project. To prepare for these conversations, Dr. Yen suggests getting out into the world and presenting your ideas to others in the entrepreneurial space. Get accustomed to being challenged and practice building your arguments.

2. “Get a cofounder” -Dr. Nathan Brown

Dr. Brown, co-founder of Parallel Health, started his company to bring personalized cosmetics to the market through phages. When asked, “What’s the best thing about starting a company,” he was quick to reply “Working with my awesome co-founder.” Building strong working relationships are critical for all, but finding your co-founding complement is one of the strongest steps forward in beginning a company. A co-founder will not only aid in divvying up the commercial tasks, but also share the mental and emotional stresses of opening a business.

3. “You need one friend who knows about startups” -Dr. Jessica Sacher

Dr. Sacher’s company, Phage Directory, was created as a “match-making” service connecting doctors and researchers with phages. The company’s mission is to facilitate access to phages for use in phage therapy and biocontrol. Throughout the panel discussion, the panelists discussed ways that they built a community around their innovations. From local entrepreneur meetups to chats with business-oriented peers and professors, our panel recommends early starters seek out advice and support from people that can connect to the entrepreneurial odyssey.

Follow Genome Startup Day on Twitter and LinkedIn for more insights on biotech startups and to be alerted of future events.

Unlock the Virome with ProxiPhage

Posted on July 26, 2021 by Benjamin Mitchell - Genomics, Metagenomics, ProxiMeta

Metagenomic studies are illuminating the diverse array of microbiomes that exist from the ocean floor to our gastrointestinal tracts. Understanding these microbial communities is essential to understanding modern health and the environment; however, outdated lab techniques are laborious, costly, and fail to create a complete picture of the microbiome. This article, posted by Ivan Liachko, describes how advancements in biotechnology are facilitating exciting discoveries with recent tools developed to capture phage and other mobile genetic element dynamics within microbiome samples.

Continue reading to discover how ProxiPhage, a recent addition to the ProxiMeta platform, is helping scientists answer questions relating to microbiome composition dynamics, prophage prevalence, frequency of transient infections, spread of antibiotic resistance, and more.

https://www.linkedin.com/pulse/unlocking-virome-proximity-guided-metagenomics-new-frontier-liachko/