Capsid and Tail

Image of Nagoya, Japan, by Kimoto from Pixabay

Issue 47 | October 10, 2019
15 min read

The Nagoya Protocol and phages: an introduction

You may have heard of the Nagoya Protocol in the context of isolating or sharing phages or bacteria. But what is the Nagoya Protocol, and how does it apply to phage research and development? This week, we’ve put together a primer to help explain it, and a bunch of resources that should help you navigate it.

Also in this issue: an exciting breakthrough in synthetic phage biology, more info on NIAID’s plans to fund phage research, prophage-antibiotic synergy, and more!

What’s New

Have an idea for us? Send us a tip!

Related to the new NIAID request for applications (RFA) for phage studies, here’s a videocast of the NIAID council meeting where they discuss their phage interests and why they’re going to fund phage studies now and in the future. Start watching at around the 1:01:00 mark; they talk about phage for around 20 min. Also, Jane Knisely is the person to email about this RFA. If you’d like to work with other phage groups to put together a proposal, email us at capsid@phage.directory and we’ll do our best to connect you with others in the same boat.

Grant FundingPhage Therapy

Kevin Yehl of MIT and colleagues have developed a high-throughput strategy to genetically engineer host range-determining regions within phage tail fiber proteins to create libraries of millions of phages with different receptor binding capacities. They showed that “phagebodies” could limit E. coli in a mouse wound infection model, and they did not observe emergence of phage-resistant strains. Cell Host & Microbe Paper | News article

ResearchPhage Engineering

Sara Clifton of the University of Illinois at Urbana-Champaign and colleagues have used population modeling to examine the role of latent prophages in bacterial populations in response to antibiotic treatment. They show that antibiotics can induce stress that leads latent prophages to control bacteria, even when the bacteria are resistant to the antibiotics applied.

ResearchPhage-Antibiotic SynergyProphage biology

Michele Mutti and Lorenzo Corsini of the phage biotech company PhagoMed have published a review on GMP production of phages for therapy. They review the literature covering technical issues and approaches to increase robustness at each step of the process, and conclude that it is possible to control cost at the same time.

Phage TherapyReviewGMP production

The Center for Innovative Phage Applications and Therapeutics (IPATH) at UCSD has published the first issue of its new quarterly newsletter. This quarter’s issue features an interview with Dr. Hedieh Attai, a postdoc at IPATH, along with info about recent funding IPATH has received. Read issue 1 and subscribe here!

NewsletterPhage Therapy

Here’s a new phage therapy podcast episode featuring Dr. Aleksandra Petrovic-Fabijan and Dr. Ruby Lin from the Westmead Institute for Medical Research in Westmead, Australia. [Medical Journal of Australia Podcast, 21 mins]

PodcastPhage Therapy

Postdoctoral position: Phage biology and applications

University of Copenhagen, Copenhagen, Denmark

The PhageBio group, Lone Brøndsted

We are looking for a highly motivated and dynamic researcher for a 2-years post doc position in Bacteriophage biology and application starting on January 1st 2020 or as soon as possible hereafter. The post doc will have a major role in testing the safety and efficacy of bacteriophages targeting porcine enterotoxigenic E. coli as a part of the AVANT project funded by the European Commission. The aim of this project is to collect pre-clinical data by testing the safety and efficacy of a phage-based product targeting porcine ETEC. You will work in the PhageBio group in Copenhagen headed by Professor Lone Brøndsted and alongside post doc Michela Gambino. For more information about our research see here. Please note that only online applications can be considered: apply here.

Post Doc Phage Biology

DOE Graduate Student Research: Soil Phages

Pacific Northwest National Lab (PNNL)

Michelle Davidson, Richland, WA

Are you interested in soil phages and inter-kingdom interactions? Apply to the DOE Office of Science Graduate Student Research Program and come collaborate with us at the Pacific Northwest National Lab (PNNL).

Award Benefits

  • A monthly stipend of up to $3,000/month for general living expenses
  • Reimbursement of inbound/outbound traveling expenses to/from the host DOE laboratory/facility of up to $2,000

Eligibility

  • U.S. Citizen or Lawful Permanent Resident
  • Qualified graduate program & Ph.D. Candidacy
  • Graduate research aligned with an SCGSR priority research area
  • Establishment of a collaborating DOE laboratory scientist at the time of application

Applications must be submitted via the official website. Please contact Michelle Davison michelle.davison@pnnl.gov to discuss potential collaborations!

Graduate Student Research Opportunity Soil phages
More Details Last day: November 14, 2019

Junior/Assistant/Associate/Full Specialist: CRISPR and phage

University of California, San Francisco

Dr. Joseph Bondy-Denomy

The Bondy-Denomy lab is seeking a Junior/Assistant/Associate/Full Specialist to join our group and contribute to new and ongoing projects. Our lab focuses on CRISPR-Cas immune systems and their natural functions in bacteria. We are also interested in developing new tools stemming from both Type I and II CRISPR-Cas systems, both for inhibitor proteins and new applications for these systems in microbes (see Bondy-Denomy et al., Nature 2015, Rauch et al., Cell 2017, Marino et al. Science 2018, Jiang et al. Mol Cell 2018).

The candidate will be expected to contribute to this tool development and CRISPR biology work in the lab, by conducting microbiology and molecular biology techniques, including bacterial and bacteriophage manipulation, cloning, protein purification, and biochemical assays. An exceptional candidate will lead their own independent project, develop new ideas, be familiar with the literature, and participate in procurement of funds, where appropriate. Additionally, the specialist will be expected to assist with managing day-to-day lab operations, and perform general lab duties and be a positive lab citizen.

Research Scientist CRISPR

Community Board

Anyone can post a message to the phage community — and it could be anything from collaboration requests, post-doc searches, sequencing help — just ask!

October 4, 2019

Seeking collaborators for phage characterization studies

Emmanuel Nnadi, Plateau State University, Bokkos, Nigeria

My lab started isolation of phages from hospital environment, so far we have isolated a phage effective against E.coli and working on phages against P. aeruginosa. As a small unfunded lab we are not able to characterize and store for very long because of electricity. So we are open to collaboration. Any lab willing to collaborate to store and characterize our phage and also open to further studies are welcome. Please email me at eennadi@gmail.com.

Phage IsolationSeeking collaborators
October 4, 2019

Looking to meet phage scientists, find companies offering EM services, and find out about phage conferences

Dr. Ritah Nakayinga, Kyambogo University, Uganda

Hello passionate phage scientists,
My name is Dr. Ritah Nakayinga and I will be starting phage research, early 2020, at Kyambogo University, Uganda. My research is funded by IDRC/OWSD. I will be developing an effective phage bio-control against the Banana wilt disease of the Banana crop and a major staple food crop in Uganda. I would like to network with phage scientists with similar research interests, get information about companies that offer affordable electron microscopy services and any upcoming future phage conferences in 2021. Reach me at: nakayingar@gmail.com.

Phage BiocontrolBanana wilt
October 4, 2019

Seeking PhD position

I have a master’s degree in microbiology. I defended my thesis with the title of ‘Isolation and Identification of Specific Viruses Isolated from the Microbial Corroded Place in the Petroleum Industry’ with the best grade. The title of one of my articles that is published in Anti-Corrosion Methods and Materials Journal is ‘Phage therapy of corrosion-producing bacterium Stenotrophomonas maltophilia using isolated lytic bacteriophages’.

I am keen to work in microbiology, bacteriophages (phage therapy) and biotechnology. Please email me at arezoopedramfar@yahoo.com if you are interested.

Phage TherapyMicrobiologyBiotech
October 9, 2019

Seeking postdoctoral position

Dr. Soleimani

I am seeking a research position in phage therapy or molecular phage studies. I hold a Ph.D from Shahid Beheshti University, Tehran, Iran (Department of microbiology and microbial biotechnology, faculty of life sciences and biotechnology).

My thesis was entitled “Isolation of a lytic bacteriophage effective against Multidrug-resistant (MDR) Klebsiella pneumoniae and the potential of phage therapy against infection in a mouse model” under the supervision of Prof. Fereshteh Eftekhar. During my Ph.D. project, I have experienced almost all the necessary techniques and methods for phage study, phage therapy and lung infection studies in animal models. I am looking for a postdoc or research scientist position. Please contact me at mah.slmn@yahoo.com.

Phage TherapyMolecular phage studies

The Nagoya Protocol and phages: an introduction

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Phage microbiologist and co-founder of Phage Directory

Co-founder

Phage Directory, Atlanta, GA, United States

Jessica Sacher is a co-founder of Phage Directory and has a Ph.D in Microbiology and Biotechnology from the University of Alberta.

For Phage Directory, she takes care of the science, writing, communications, and business aspects.

What is the Nagoya Protocol?

It’s an international treaty that aims to promote conservation of biodiversity by making sure that countries rightfully benefit from their own biological (genetic) resources. Its full name is the ‘Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits Arising from their Utilization to the Convention on Biological Diversity’. Essentially, genetic material is property of the country of origin. As you may have guessed, this applies to phages.

When did it come into effect?

The Nagoya Protocol was adopted in 2010, and took effect in 2014. The UN Convention on Biological Diversity was signed in 1992, and the Nagoya Protocol was meant to be a harmonized way of implementing part of what came out of the Convention on Biological Diversity.

What does this mean?

Essentially, the collection and use of biological/genetic resources needs to be approved by the country of origin. This means it can be illegal to even take samples from a country and not report it to that country, even if the samples will only be used for research, and even if they will merely be classified and stored.

How does reporting work?

Reporting can take many forms, and differs from country to country. Each country gets to make up its own terms and enforce everything themselves. So if you’re planning to sample from a given country, you should use this tool to look up that country’s Nagoya requirements before sampling.

This sounds like a lot of paperwork

It can be. Some feel that the Nagoya Protocol hinders biological research and development of products from biological entities (ahem: phages).

“In principle, every scientist is obligated to personally determine what applies in a country and which permits need to be obtained,” Professor Jörg Overmann, Managing Director of the DSMZ, says. “The Nagoya Protocol has made it considerably more difficult for science to work with bacteria or fungi cultures, which are among the most utilizable resources in the life sciences. Many underestimate the additional effort of obtaining Nagoya-related permission.” — 2018 DSMZ Press Release

The DSMZ’s progress toward streamlining Nagoya compliance

The DSMZ, a publicly-funded culture collection in Germany (which includes phages; see our previous Capsid & Tail post on phage banks here), has actually taken steps to make compliance with the Nagoya Protocol easier for people who deposit and order phages from their repository.

Fun fact: the DSMZ is the only organization in the European Union to appear as a “Registered Collection” in regards to Nagoya Protocol compliance. This means the DSMZ has demonstrated that it can handle the Nagoya requirements and that people who obtain samples from them can be confident that the agreements they sign with the DSMZ are sufficient to comply with Nagoya. You can read more here in this paper authored by the DSMZ director, Jörg Overmann or in this 2018 DSMZ press release.

Criticism of the Nagoya Protocol (as it applies to microbiology)

The Nagoya Protocol arose out of concern for larger species going extinct, paired with concern that developing countries (considered hotspots of biological diversity) would be taken advantage of by industrialized countries seeking to commercialize their genetic resources. Jörg Overmann and Amber Hartman Scholz of the DSMZ made a few key arguments regarding why the Nagoya doesn’t make as much sense for microbes.

In brief, they argue that microbial diversity is so vast and microbes are so distributed and cosmopolitan that microbial diversity hotspots aren’t necessarily located in developing countries (they state that 1 g of soil from North America or Europe contains 5 times as many microbial species as have been validly described in total). They also point out that microbes are in essentially unlimited supply, and not at risk of going extinct. From an economic perspective, they argue that microbes and their DNA aren’t inherently very valuable; rather, it takes so much work to isolate and characterize them that the bulk of their value lies with the research done and not with the genetic material itself.

All in all, the authors argue that the Nagoya Protocol should be carefully applied when it comes to restricting access to microbial resources, and that countries who apply the directives of the protocol with microbe-specific principles in mind will enjoy profound benefits compared to those who don’t.

How many countries have ratified the Nagoya Protocol?

Over 100 countries have ratified it, and are thus “party to” the Nagoya Protocol.

Examples of countries who are party to the Nagoya Protocol:

  • The European Union
  • Many countries in Africa
  • Many countries in Asia
  • Many countries in South America
  • India

Examples of countries that are NOT party to the Nagoya Protocol:

  • USA
  • Canada
  • Australia
  • Georgia
  • Many countries in the Middle East

A caveat: countries that haven’t ratified Nagoya may still impose restrictions

Even countries who haven’t signed the Nagoya Protocol may have their own laws surrounding what can be done with biological or genetic resources sampled from their country. Brazil is an example of this. This means that seeing that a country is NOT on the Nagoya list doesn’t mean you’re home-free to sample from that country.

So what should I do?

If you work with phages, bacterial strains, DNA samples, or any other genetic resource, make sure you know the Nagoya Protocol status and requirements of the country of origin of your samples. Get in touch with the contact person or department responsible for overseeing Nagoya Protocol compliance (these are listed on the ABS Clearinghouse website) and find out what you need to do to legally isolate and process your samples.

Where can I find out more?

Acknowledgements

A special thanks to Dr. Christine Rohde of the DSMZ for raising the issue of the Nagoya Protocol when it comes to phage research and phage exchange, and for directing me to many of these relevant resources!

Do you have firsthand experience with the Nagoya Protocol?

If so, please email us at capsid@phage.directory. We’re keen to hear about how it impacts phage researchers and phage companies in the real world. We want to support phage sharing and international research, development, and collaboration, and a better understanding of how the Nagoya Protocol impacts you will help us create resources to help you and others navigate it as efficiently as possible.

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