Professor Peter Fineran, School of Biomedical Sciences: World-leading research in Phage and CRISPR-Cas systems

Professor Peter Fineran.

Participants interviewed for the case study

Principal investigator

Professor Peter Fineran
Department of Microbiology and Immunology, School of Biomedical Sciences

Researchers

Dr Rebekah Frampton
Research Associate, Plant & Food Research
Former University of Otago PhD student

Assistant Professor Raymond Staals
University of Waginengen, The Netherlands Former University of Otago postdoctoral fellow

Associate Professor Stan Brouns
University of Delft, The Netherlands

Assistant Professor Richard Scheltema
University of Utrecht, The Netherlands

Stakeholders

Dr Andrew Pitman
Fformer Team Leader at Plant and Food Research
Now General Manager at the Foundation for Arable Research

Dr Sonia Whiteman
Innovation Team Leader, Protect Supply at Zespri International Limited

Associate Professor Stan Brouns Delft
University of Technology, The Netherlands

Summary of the impact

Professor Peter Fineran leads a research group in the Department of Microbiology and Immunology at the University of Otago. The impact of his internationally-renowned research has been to advance knowledge of how CRISPR-Cas systems are regulated, and how they work as 'molecular scissors' to cut genes.

Peter has also had impacts in increasing public knowledge of science and building capability of students and scientists in the CRISPR-Cas arena. Applications to industry, as evidenced by his work on bacteriophage strategies to manage the Psa infection in kiwifruit, have also been impacted by Peter's research. Peter's success has come through high- quality research disseminated widely to the scientific community and public, as well as close collaboration with industry.

Underpinning research

Professor Peter Fineran's main research interests are the bacteriophage-resistance mechanisms of bacteria. Bacteriophages (also known as phages) are viruses which infect bacteria¹. Bacteria have their own 'immune systems' called CRISPR-Cas, just as humans have theirs. The bacterial CRISPR-Cas systems destroy invading phages and can also prevent bacteria from acquiring antibiotic-resistance genes.

Peter's main research goal is to understand the interactions between phages and their bacterial hosts. This involves understanding how these CRISPR-Cas immune systems work, including when bacteria use this immune response, how bacteria are able to communicate with each other, and how they gain 'memory' of phage attack. Peter is also interested in the potential real-world applications of phages, such as their use as antimicrobial agents. Peter's world-leading work has shown how CRISPR-Cas systems are regulated, and how they work as 'molecular scissors' to cut genes.

CRISPR-Cas systems are used for gene editing, diagnostics, regulating gene expression and related technologies¹, with the potential for a wide variety of applications in other research, biomedical therapies, and genomic editing of organisms.

The extension of CRISPR tools into human genome editing has fundamental ethical issues, which are currently being debated amongst scientists and the public³. Peter has been a public figure in these discussions, such as by participating in public talks⁴.

Currently, Peter is investigating the potential use of phages as a biocontrol agent against the Pseudomonas syringae pv. actinidiae (Psa) pathogen. Psa is a bacterium which causes kiwifruit canker. It was first discovered in New Zealand in November 2010 and in 2011 Peter started working with Zespri International Limited, the world's largest marketer of kiwifruit to develop phage-control strategies.

Funding

Peter's work has had over $6 million to date from a number of funders, including:

• Rutherford Discovery Fellowship and Marsden Fund, Royal Society Te Apārangi
• Zespri International Ltd.
• Tertiary Education Commission, NZ, via the Bio-Protection Centre of Research Excellence
• European Research Commission, European Union
• Ministry for Business Innovation and Employment

Collaborations

Peter has extensive collaborations – 12 national collaborators from eight organisations, and 15 international collaborators from nine institutions in six different countries.

Research snapshot

• Peter has produced 46 publications on phage and/or CRISPR-Cas systems, cited 2070 times in Scopus and averaging 46 citations per publication.
• Peter has been involved in producing documents designed to provide information to the public, such as the Royal Society fact sheet on gene editing².
• Peter has contributed to submissions to Government with the aim of influencing science policy, e.g. a response to the National Statement of Science Investment draft in 20146, and the Ministry of Business, Innovation and Employment's The Impact of Science in 2017⁷.
• Peter has been an invited presenter at ~25 conferences (mostly international).
• Peter participates in events to engage the public in the science around CRISPR technology, including a panel discussion at the LATE at the Museum event at Auckland Museum, also broadcast on Radio New Zealand^4,5.
• Peter is regularly called on by the media to comment on CRISPR technologies. A recent example was the New Zealand Geographic in 2017⁸.
• Peter has talked to Members of Parliament as part of the Science Speaker Series discussing CRISPR technologies.
• 12 of Peter's articles on CRISPR-Cas and phage have been cited in 58 granted patents.

Recognition

Peter has received a number of international and national awards, including:

• 2019 Alexander von Humboldt Experienced Researcher Fellowship, Germany
• 2019 Fleming Prize, Microbiology Society, UK
• 2017 Genetics Society of AustralAsia Ross Crozier Medal
• 2017 Andrew Shelling Trophy, NZ
• 2015 NZ Society for Biochemistry and Molecular Biology Custom Science Award
• 2015 Thermo Fisher Scientific Award, for Excellence in Molecular Biology, NZ
• 2012 Rutherford Discovery Fellowship, Royal Society of New Zealand

Details of the impact

Advancing knowledge

• Peter's work has advanced scientific knowledge around the role of CRISPR-Cas defence mechanisms of bacterial populations, enabling further research and development to take place in the field.
• Through wide dissemination of his work, Peter is now recognised amongst scientists as an expert on CRISPR-Cas, increasing the reputation of the University of Otago.
• Peter's public outreach has increased knowledge of CRISPR-Cas technologies in the public domain. Due to the potential ethical implications of CRISPR technologies it is important the public is well informed and takes part in decision-making.

Building capability

• Over 50 students and staff have trained and worked in the Peter's lab in the past 10 years, expanding their knowledge and research capability. A number have gone on to run their own laboratories overseas.
• Capability development increases the potential for translation to other aspects of basic science, for example findings on the phage mechanism of Psa may be transferred to other bacterial pathogens of medical importance.
• The movement of trained staff to other institutes has enabled phage and CRISPR research to be undertaken in organisations where there was previously no capacity in this area. For example, Dr Rebekah Frampton moved from Peter's lab to Plant & Food Research, which has enabled students and technicians in the organisation to build their capability with CRISPR technology.

Translation to applications

• With regard to Psa, Peter's CRISPR research is allowing the development of phage-control strategies to be tailored and applied in a more specific manner. This may ultimately lead to better crop yields and associated economic impacts. There are also potential environmental impacts as it would reduce the use of harmful agrichemicals and antibiotics, ultimately preventing antibiotic-resistance, one of the biggest threats to the world's food security⁹.
• CRISPR-Cas mechanisms are now used as DNA editing tools in research environments. These tools have accelerated research into treatments for certain human genetic disorders such as sickle cell anaemia The rapidly-expanding biotechnology industry built on CRISPR-Cas genome editing now exceeds one billion US dollars, and Peter's research has broadly informed this work.

“CRISPR tools now are being applied across all different research areas of biology. So, anyone who wants to understand how any organism works, can now use CRISPR to mutate or control a particular gene. There's huge impact from that.”

Professor Peter Fineran – Department of Microbiology and Immonology, School of Biomedical Sciences

Pathway to impact

Characteristics of the research

• Peter has created his own niche in the field by undertaking novel research. This has allowed him to generate impact in a highly competitive area of research.
• The research programme is highly cohesive with all projects interconnected into the theme of phage-bacterial interactions. This allows the scientists to collaborate, help each other, troubleshoot, and share what works.
• The research is scientifically excellent, making it of high value to other scientists and stakeholders. For example, 58 granted patents cite Peter's research.
• The choice of research that is applicable to multiple areas (e.g. biotechnology, agriculture, human health, society) has allowed it to have widespread actual, and potential, impact.

Engagement

• Peter has actively sought engagement with industry. He approached the industry stakeholder Zespri after the 2010 Psa outbreak and they agreed to fund this work.
• Engagement with the public has been important for increasing understanding and awareness of the role of science in society. This engagement has provided Peter with feedback on his research, allowing him to understand different perspectives on his research, and gauge the interest in his work.
• Peter has met with kiwifruit growers to gain insight into the environment in which the research is hoped to provide impact.
• Taking media opportunities as they arise has been important for disseminating the research message.

“Unintended things – those won't happen if you don't engage. If you just sit in your lab, sit in your office, those doors won't open.”

Professor Peter Fineran – Department of Microbiology and Immonology, School of Biomedical Sciences

Dr Sonia Whiteman.

• Relationships with organisations that are potential avenues for delivering impact, such as Plant & Food Research and Zespri, have been prioritised.
• Peter utilises people close to the end-user (for example, Dr Sonia Whiteman from Zespri), understands their strengths and involves them in discussions, thereby creating teams of people involved in creating impact.
• Attending and presenting at conferences has been an excellent tool for keeping up to date with advances in the field and setting up new collaborations.
• Sharing lab meetings with researchers from other areas is a good way of being exposed to different research perspectives.
• Peter works with overseas groups to undertake research for which there is currently no technological capability in New Zealand. For example, collaborating with Associate Professor Richard Scheltema and Professor Albert Heck's world-leading proteomics laboratory in The Netherlands (University of Ultrecht) has enabled the study of protein complexes and Cas protein complexes by mass spectrometry and crosslinking.

Communication skills

• Strong communication skills have been important for building networks and relationships.
• Clear communication with end-users has been vital. This includes being honest about limitations, being open to constructive criticism and allowing end-users the opportunity to make informed decisions.
• Presenting research in a way that is understandable to a non-specialist audience is important when engaging with stakeholders and the public.

“Have a good story. You've got to connect with the people who are funding you, and with who it's going to make a difference to.”

Dr Rebekah Frampton – Research Associate, Plant & Food Research

What next?

• The ultimate aim of the Psa research is to create a product to control or eliminate Psa. This will require a commercialisation process, and finding a pathway to market which may result in economic benefit for the researchers and stakeholders.
• Research will continue into understanding how CRISPR systems work and how they can be exploited. This has potential impact for understanding and halting the spread of antibiotic resistance.
• Within the team, there is opportunity to develop new diagnostic tools around CRISPR-Cas, and move into the applied space.

References

1. Fineran PC. Resistance is not futile: Bacterial 'innate' and CRISPR-Cas 'adaptive' immune systems. Microbiology. 2019;165(8).
2. Royal Society of New Zealand. Gene editing: Evidence update.
   https://royalsociety.org.nz/assets/documents/Gene-editing-evidence-update2.pdf
3. Brokowski C, Adli M. CRISPR Ethics: Moral considerations for applications of a powerful tool. Journal of Molecular Biology. 2019;431(1):88-101.
4. Auckland Museum. LATE 2018 - CRISPR - Utopian or Dystopian? Post-Nature 2018
   https://www.aucklandmuseum.com/visit/whats-on/lates/late-crispr
5. Radio New Zealand. A panel discussion on gene editing, ethics and whether you should do something just because you can. 2018.
   https://www.rnz.co.nz/national/programmes/smarttalk/audio/2018675075/a-panel-discussion-on-gene-editing-ethics-and-whether-you-should-do-something-just-because-you-can
6. Ministry of Business Innovation & Employment. Submisions on the draft National Statement of Science Investment 2014.
   http://www.inovasyon.org/pdf/NewZealand.summary.of.submissions.on.the.draft.pdf
7. Ministry of Business Innovation and Employment (MBIE). Impact of science: Discussion paper: summary of submissions 2017.
   https://www.mbie.govt.nz/assets/125386605f/impact-of-science-discussion-paper-summary-of-submissions.pdf
8. Evans K. Life Hackers. New Zealand Geographic 2017; (148).
   https://www.nzgeo.com/stories/life-hackers/
9. World Health Organisation. Antibiotic resistance 2018.
   https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance