Monitoring the Ecology vs. Evolutionary Biology of Phage Resistance: A Tale of Two Precisions

Stephen T. Abedon

Department of Microbiology – The Ohio State University

phage.org – phage-therapy.org – biologyaspoetry.org


An important question for those with ecological and evolutionary biological interests is when a given situation is of ecological relevance vs. when it might be more of evolutionary biological importance (Abedon, 2022b). Telling the difference can be important for all of us.

Ecology by definition is the interaction of organisms with their environments.

We can describe phage use as antibacterial agents, that is, phage therapy, as an example of community ecology, or more precisely an applied community ecology. This is community ecology because there is more than one species of organism involved, i.e., as making up an ecological community. Minimally this is the phage (species #1) and the targeted bacterium (species #2), but also of importance is the treated body (species #3).

By definition, bacterial resistance to phages is ecological, as it describes a specific type of interaction, in this case between at least two species, the phage and the bacterium. That the resistance ‘interaction’ is one of ‘non-‘ or ‘less-‘ contact by the bacterium with the phage antagonist is only a detail, just so long as this lack of interaction is phenotypic, i.e., as opposed to the phage and bacterium instead just happening to exist in different places.

Bacterial resistance to phages also of course can have evolutionary aspects.

Evolution by definition is a change in allele frequencies in at least one species, or, more precisely, changes in allele frequencies in one population, in either case as observed over time.

Often the changes in allele frequency that we care most about are consequences of the impact of natural selection, and natural selection under most circumstances has a strong ecological component. Indeed, natural selection in most cases can be defined as the impact of ecology on evolutionary biology (and hence, as an aside, the existence of the science of evolutionary ecology).

By definition yet again, changes in the frequency of phage-resistance alleles within a bacterial population is an evolutionary process and typically these changes are a consequence of natural selection. The selective agent would be that phage population that is negatively affecting a bacterial population, resulting in increases in the frequency of whatever bacterial alleles are conferring protection from this phage.

Of interest to phage therapy is that this ecology driving evolutionary biology can in turn drive ecology. Specifically, once the frequency of alleles conferring phage resistance are high enough within a targeted bacterial population, then the applied community ecology of phage therapy can be affected, e.g., phage therapy can stop working.

In addition, if the frequency of a phage-resisting allele is found to be 100% within the bacterial population, following phage treatment (i.e., a frequency of 1.0), then if nothing else this is indicative that bacterial survival – an ecological issue – in this instance likely is a function of the occurrence of phage resistance.

If the frequency of phage resistance instead is 0% following phage treatment (0.0), then if nothing else this is indicative that bacterial survival (again, an ecological issue) was not a function of the occurrence of phage resistance. In fact, any frequency of phage resistance below 100% within a targeted bacterial population means that phage-sensitive bacteria are persisting despite phage treatment. For an example of the latter, see, e.g., Box 2 of Abedon (2022c).

Phage-resistant bacteria may display reduced virulence against bodies or may be subsequently treated with a different phage. Consequently, in some ways phage-resistant bacteria are not necessarily that big of a deal as a midpoint of a phage treatment, and this can be particularly if a diversity of other treatment phages are available. Phage resistance is not desired nor welcome, of course, but evolution of phage resistance also is not a certain indication of phage therapy microbiological failure.

That, by the way, to a degree contrasts with the evolution of antibiotic resistance that can occur over the course of antibiotic treatments, which can indeed be associated with treatment failures with high likelihood. One difference is something called antagonistic pleiotropy – not to be confused with antagonistic coevolution (Abedon, 2022a)!!! – i.e., whether or not resistance alleles are otherwise costly to the carrying organism (Abedon, 2022d). If resistance is both easily attained and not ecologically costly, then, well, that can be problematic, particularly given only mono therapies. Another difference is the sheer abundance of diverse, typically safe-to-use phages that often can be available to phage therapists (Abedon and Thomas-Abedon, 2010).

In any case, the persistence of phage-sensitive bacteria despite phage treatment probably means that, for whatever reason, treatment phages are not able to successful infect targeted bacteria despite those bacteria being phage sensitive; again, see Box 2 of Abedon (2022c). This frankly should be viewed as a big deal as essentially by definition it implies a phage therapy microbiological failure, one that may or may not be easily rectified, or at least a lack of complete eradication of phage-sensitive bacteria. I mean, how does one deal with phages not being able to easily reach and/or kill the otherwise phage-sensitive bacteria they are targeting?

Perhaps, as an answer to that question, some other phage that happens to be able to do a better job of reaching and/or killing those otherwise phage-sensitive bacteria might be available for use. That certainly is possible, but at this point in time we really aren’t all that good at figuring out what might constitute a better phage for phage therapy, other than in terms of host range – though see for example Bull et al. (2002; 2019) – and particularly better than the phage that we started with, presumably assuming that the first phage tried we thought was the better phage for phage therapy, hence why it was used first.

Of course, we almost take it as a matter of faith that phage carriage of extracellular polymeric substance (EPS) depolymerases (Danis-Wlodarczyk et al., 2021b) will solve many problems of phage penetration to targeted bacteria. But whether that is actually true in all instances, e.g., such as phage distribution throughout lungs – yet again, see Box 2 of Abedon (2022c) – is in my opinion just not known.

How might use of a phage cocktail instead result in complete eradication of a phage sensitive bacteria when a monophage does not? Just better odds that at least one of the phages used will be particularly good at achieving this? As another aside (Danis-Wlodarczyk et al., 2021a; Abedon, 2022c), note that it can be helpful to just apply a phage or phages at higher or multiple doses before giving up on a given treatment strategy!

At any rate, not being able to eradicate bacteria from an infection even though those bacteria are sensitive to a given treatment can be a far greater problem than failure that get rid of bacteria that explicitly are not susceptible to a treatment protocol. That is, there exits a basic problem in the applied ecology of treatments if not even phage-sensitive bacteria can be removed in full, just as there is a basic problem for an antibiotic treatment if the antibiotic is unable to fully eliminate even antibiotic-sensitive bacteria, a.k.a., the concept of antibiotic tolerance. For a bit on the latter, see Appendix A1 of in fact yet yet again, Abedon (2022c).

So where exactly am I going with this? At the end of a phage treatment, it is important to know whether the frequency of phage-resistant bacteria among the targeted bacterial population is high (at or approaching 100%) rather than low (near 0%). But high precision in that measurement, e.g., more than just whole percentage-point differences, really is not all that important. Why not?

Especially ecologically, there likely is little difference between 0.1%, 0.01%, or even maybe 10% or 50% of the bacteria being phage resistant, as that will still leave an awful lot of phage-sensitive bacteria having escaped phages during treatment. At some probably higher frequency of phage resistance we might come to feel that the frequency of remaining phage-sensitive bacteria is less important, but exactly where that point lies is difficult to say. My gut feeling, though, is that at the point where we start having to do statistics to tell the difference, i.e., at a point where higher precision in measurements becomes important, the importance of differences in the frequencies of phage-resistant bacteria – 100% or a tiny bit less than 100% – probably are no longer all that relevant. (For consideration of the statistics of plating-based enumeration, see Abedon and Katsaounis, 2021.)

Ah, you are saying, clearly therefore I am leading up to claiming that if we are interested instead in the evolutionary biology phage resistance, then in that case we really should care about measuring resistance frequencies with higher precision. And you would be absolutely right!  Except also maybe not.

The problem here is that a key word in the definition of evolution that we are using is “Change”, and by definition change cannot be measured using only a single data point, or in the case of quantifying evolutionary change, a single time point. Thus, no matter how precisely you measure the endpoint frequency of phage-resistant bacteria, that will not tell you that evolution has occurred in the course of phage therapy treatment, much less how much evolution.

Here is the basis of this latter point: At the start of an experiment, if your population of bacteria ever is going to contain phage-resistant members, then it likely already does contain those mutants (this, by the way, is why only-qualitative determinations that phage resistance is present, e.g., such as following phage treatments, are basically meaningless). Exceptional would be if the starting number of bacteria involved is so low that this number is, e.g., less than the inverse of the rate of mutation to phage resistance. Thus, for every time a bacterium divides, let’s say that there is a probability of 10-5 that a mutation to phage-resistance will occur. If so, then in a population of 106 bacteria, on average 10 phage-resistant bacteria will be expected to be present, more or less (Abedon et al., 2021).

That last part, “More or less”, is crucial, however, as the frequency with which mutations conferring phage resistance are expected to be present is predicted to somewhat “Fluctuate” about an average (Luria and Delbrück, 1943). In practice, this means that even if you precisely know bacterial rates of mutation to resistance to a given phage, you still will not know how many phage-resistant bacterial mutants will be present prior to the start of treatments. (As yet another aside, actually calculating mutation rates, vs. just mutant frequencies, is a not trivial thing to do.)

Without knowing the frequency of phage resistance prior to the start of treatments, then you are only really guessing whether evolution has occurred in the course of a phage treatment, no matter how precisely frequencies of phage resistance may be measured after a treatment is done.

In short, ecologically, the precision of measures of frequencies of bacterial phage resistance need not be all that high to possess high value in understanding the outcome of phage treatments. I mean, either phage-sensitive bacteria have persisted despite prior treatments or they have not, without a need to describe percentages with precision past the decimal point. Thus, 50.0% vs. 50.1%? Who cares? Indeed, 50% vs. 51%, who cares?

Alternatively, if one really cares about being precise in monitoring the evolution of phage resistance, then the most important place to emphasize that precision actually should be prior to the start of treatments, i.e., prior to initial phage application, and only then should one be measuring frequencies of phage resistance after treatments as well. But don’t forget that you need to have this information for explicitly that bacterial culture that is being treated, since evolutionarily all we really will care about is how a specific bacterial culture as a population changes in allele frequencies over time, and in phage therapy that bacterial population is precisely the one that you are treating.

Even so, how much more than order-of-magnitude precision do we really need in monitoring the evolution of phage resistance during phage treatments? Will we really care for example if the frequency of phage-resistant bacteria have changed from 10-5 to 10-5.5? And how hard would we have to try to be sure that such a relatively small change is actually real? I mean, seriously, except for the most hard-core evolutionary experiments, who would really care?

For what it is worth, when I look at the outcome of a phage treatment, if all of the targeted bacteria remaining are phage resistant, then I know what went wrong (clue: the bacteria have evolved resistance to the treatment phages, i.e., an evolutionary outcome). But when I look at the outcome of a phage therapy experiment and a substantial portion of the bacteria remaining are still phage sensitive, then more often than not I can only speculate as to what might have gone wrong, except again for those bacteria that have evolved phage resistance (Abedon, 2022c).  Still, this latter scenario should be viewed at least as an ecologically relevant outcome.

But bottom line: Obtaining an additional decimal place or two in describing the frequency of phage-resisting alleles within the treated bacterial population generally will not greatly aid in improving the precision of our applied ecological speculation.

Afterthought:

You would think that this essay came into existence as a natural outgrowth of the cited publications, particularly Abedon (2022c), but you would be wrong! On the other hand, I did wait a few months until that publication was published and available open access. Thanks for your interest!

Literature Cited:

Abedon, S. T. 2022a. A primer on phage-bacterium antagonistic coevolution, p. 293-315. In Bacteriophages as Drivers of Evolution: An Evolutionary Ecological Perspective. Springer, Cham, Switzerland. https://link.springer.com/chapter/10.1007/978-3-030-94309-7_25

Abedon, S. T. 2022b. Frequency-dependent selection in light of phage exposure, p. 275-292. In  Bacteriophages as Drivers of Evolution: An Evolutionary Ecological Perspective. Springer, Cham, Switzerland. https://link.springer.com/chapter/10.1007/978-3-030-94309-7_24

Abedon, S. T. 2022c. Further considerations on how to improve phage therapy experimentation, practice, and reporting: pharmacodynamics perspectives. Phage 3:95-97. https://www.liebertpub.com/doi/full/10.1089/phage.2022.0019

Abedon, S. T. 2022d. Pleiotropic costs of phage resistance, p. 253-262. In Bacteriophages as Drivers of Evolution: An Evolutionary Ecological Perspective. Springer, Cham, Switzerland. https://link.springer.com/chapter/10.1007/978-3-030-94309-7_22

Abedon, S. T., and C. Thomas-Abedon. 2010. Phage therapy pharmacology. Curr. Pharm. Biotechnol. 11:28-47. https://pubmed.ncbi.nlm.nih.gov/20214606/

Abedon, S. T., and T. I. Katsaounis. 2021. Detection of bacteriophages: statistical aspects of plaque assay, p. 539-560. In D. Harper, S. T. Abedon, B. H. Burrowes, and M. McConville (ed.), Bacteriophages: Biology, Technology, Therapy. Springer Nature Switzerland AG, New York City. https://link.springer.com/referenceworkentry/10.1007/978-3-319-40598-8_17-1

Abedon, S. T., K. M. Danis-Wlodarczyk, and D. J. Wozniak. 2021. Phage cocktail development for bacteriophage therapy: toward improving spectrum of activity breadth and depth. Pharmaceuticals 14:1019. https://pubmed.ncbi.nlm.nih.gov/34681243/

Bull, J. J., B. R. Levin, T. DeRouin, N. Walker, and C. A. Bloch. 2002. Dynamics of success and failure in phage and antibiotic therapy in experimental infections. BMC Microbiol. 2:35. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC138797/

Bull, J. J., B. R. Levin, and I. J. Molineux. 2019. Promises and pitfalls of in vivo evolution to improve phage therapy. Viruses 11:1083. https://pubmed.ncbi.nlm.nih.gov/31766537/

Danis-Wlodarczyk, K., K. Dabrowska, and S. T. Abedon. 2021a. Phage therapy: the pharmacology of antibacterial viruses. Curr. Issues Mol. Biol. 40:81-164. https://pubmed.ncbi.nlm.nih.gov/32503951/

Danis-Wlodarczyk, K. M., D. J. Wozniak, and S. T. Abedon. 2021b. Treating bacterial infections with bacteriophage-based enzybiotics: in vitro, in vivo and clinical application. Antibiotics 10:1497. https://pubmed.ncbi.nlm.nih.gov/34943709/

Luria, S. E., and M. Delbrück. 1943. Mutations of bacteria from virus sensitivity to virus resistance. Genetics 28:491-511. https://pubmed.ncbi.nlm.nih.gov/17247100/

Phage Futures Congress 2019 | January 29-30 2019 | Washington D.C., USA

With antimicrobial resistance a rising global crisis, western medicine’s interest is turning to phage therapy as an alternative to antibiotics. Challenging past uncertainty in phage therapy’s commercial viability, recent developments such as highly positive results of compassionate use cases in the US has excited the field and the next step is successful phase II clinical trials.

Phage Futures Congress is a translational phage therapy conference where Steffanie Strathdee, Tom Patterson, the FDA, and others will discuss how we move phage therapy forward in the US. A number of A Smaller Flea authors will be speaking or in attendance: Jessica Sacher of Phage Directory, Ben Chan of Yale Univeristy, Shawna McCallin of PhageForward. I am pleased to announce that I have also joined the Scientific Advisory Board for the congress

Take a look at the agenda here.

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Senior Research Assistant – Northumbria University

We are now seeking applications from highly committed, motivated and talented postdoctoral researchers to join the phage research team at Northumbria University for a fixed term, 24 months project in collaboration with clinicians at the Great Northern Children’s hospital, Newcastle upon Tyne. This Action Medical Research funded project will characterise the intestinal virome of preterm, low-birthweight infants to determine bacteriophage groups that are present in the early gut flora in neonates.

Continue reading

Eligo Bioscience is hiring

“Eligo Bioscience is a VC-backed biotech startup, cofounded by professors and scientists from MIT and Rockefeller (Lu and Marraffini labs). We are developing next-gen therapeutics for precision microbiome engineering and bacteria-associated diseases. Our technology is based on the delivery of genetic circuits (notably CRISPR-Cas) to the microbiome via engineered phage particles.” They can be contacted here.

ii_15fc434b23801095

Postdoctoral Researcher in Foodborne Pathogen Bioinformatics

Responsibilities:
Work with microbiologists to develop a pipeline for analysis of Campylobacter spp. whole genome sequencing data. This will involve processing of raw sequencing reads, genome assembly, submission of data to public databases, variant mapping, and phylogenetic analysis. The individual will also work with public health professionals at the Tennessee Department of Health (TDH). The role in this joint effort will be to provide data based on outputs from the pipleline, which will inform TDH investigations of campylobacteriosis within Tennessee. Additionally, the individual will assist with knowledge transfer by participating as part of a team in workshop and webinar development and delivery.

Required Qualifications: An earned doctorate in Bioinformatics, Computational Biology, Statistics, Microbiology, Food Science, or other relevant field. Demonstrated knowledge of bioinformatics and basic knowledge of relevant computer programming languages (such as Python, Perl, Bash, R, etc). Proven excellence in verbal and written communication skills, including a strong scientific, peer-reviewed publication record in bioinformatics and/or computational biology-related topics. Communicate effectively with non-computational researchers and be time-responsive

Application:

The University of Tennessee, Institute of Agriculture is seeking candidates who have the ability to contribute in meaningful ways to the diversity and intercultural goals of the University. Applicants should submit: 1) a letter of application, 2) a curriculum vitae detailing education background qualifications, research and teaching experience, and publications, 3) unofficial transcripts of all college course work, and 4) names and contact information (including e-mail addresses) of three individuals who will serve as references.

Submit all application materials using the following link:
https://ut.taleo.net/careersection/ut_knoxville/jobdetail.ftl?job=17000001BA&tz=GMT-04%3A00

More information can be found in this flier here

Opportunités de carrière : Doctoral Student SNSF (12249)

Introduction

The University of Lausanne is a higher teaching and research institution composed of seven faculties where approximately 14,300 students and nearly 3,900 collaborators, professors, and researchers work and study. Ideally situated along the lake of Geneva, near Lausanne’s city center, its campus brings together over 120 nationalities.

Presentation

The Department of Fundamental Microbiology offers a position of Doctoral Student SNSF (on bacteriophage therapy for Staphylococcus aureus infections).

Job information

Expected start date in position : 01.01.2018

Contract length : 1 year, maximum 4 years

Activity rate : 100%

Workplace : University of Lausanne until 31/12/2018 and then either in Lausanne or at the Bern University Hospital – Department of Intensive Care Medicine.

Your responsibilities

The Resch group (https://www.unil.ch/dmf/en/home/menuinst/research-units/gregory-resch.html) aims at developing new therapeutic phages and phage-lysins in a rational approach. Specifically, we isolate new bacteriophages active against the ESKAPE pathogens and evaluate their efficacity in different rodent models of infectious diseases amongst which infective endocarditis in rats. We also address fundamental aspects of phage-bacteria interactions such as bacterial resistance to phages and phage adaptation. The research project of the Doctoral Student SNSF will be on the development of new S. aureus therapeutic phages with a focus on the study of resistance mechanisms. A wide array of methods and technologies in microbiology, phage research and genomics will be applied. The project will provide an excellent scientific training with many opportunities for collaborations in a stimulating environment.

Your qualifications

Applicants should have a Master in biological science with experience in microbiology. Further experience with bacteriophages, animal experimentation, molecular biology, bacterial genomics and computational biology is an asset. The candidate should have a good command of English and be highly motivated to learn new experimental techniques to study phage-bacteria interactions.

What the position offers you

We offer a nice working place in a multicultural, diversified and dynamic academic environment, opportunities for professional training.

Possibilities of continuous training, a lot of activities and other benefits to discover.

Contact for further information

Dr. Grégory Resch

Phone number : 0041 21 692 56 09

Your application

Deadline : 30.11.2017

Please include your full application (motivation letter, CV, list of publications and the contact details of two referees) in Word or PDF.
Only applications through this website will be taken into account.

We thank you for your understanding.

Additional information

Seeking to promote an equitable representation of men and women among its staff, the University encourages applications from women.

PhD SCHOLARSHIP – VIRUS STRUCTURE, Massey University, New Zealand

Project title: Solving the end-cap structure of a biological nanorod derived from the Ff bacteriophage (f1, M13 or fd)

Academic mentors: A/Prof Jasna Rakonjac; A/Prof Andrew Sutherland-Smith

This project aims to determine the cap structure of a versatile biological filament (Ff filamentous bacteriophage). Ff (M13, f1 or fd) phage is a natural and affordable platform for a wide array of technologies, from nano-scale batteries to cancer therapies and treatment of Alzheimer’s disease. Detailed structure of the end-caps will help understand how the Ff filamentous phage is formed naturally and will aid in developing/improving filamentous phage applications.

Fig1
The fine structure of the Ff end-caps has remained a mystery, as they constitute only 2% of the phage filament mass. We overcome this problem by assembling short rods (we named Ff-nano) where the end-caps amount to as much as 40% of the total particle mass. An interesting property of the Ff-nano particles is that they easily form 2D crystals. The Ff-nano particles will therefore enable analyses of the end-cap structure at a near-atomic resolution using cryo-electron microscopy and at atomic resolution using X-ray crystallography.

Fig2
Candidates with a BSc or MSc degree (1st class or high upper 2nd class Honours degree) in biochemistry, biotechnology, molecular biology or microbiology, with interest in structural biology, bacteriophage or nanotechnology are encouraged to apply.

Scholarship is for three years, covering the stipend (NZ$ 25,000 per annum, non-taxable), fees (tuition) and medical insurance. Palmerston North is a lively student city in the Central North Island, close to the ski fields, kayaking and fishing spots, beaches and tramping areas, as well as to Wellington, the New Zealand Capital.

Institute of Fundamental Sciences at Massey University is equipped with a modern structural biology suite and has access to the Australian Synchrotron.

The deadline for the application is 08/05/2017. Applications will be considered on a rolling basis until the studentship is filled.

Filamentous phage topic:
http://journal.frontiersin.org/researchtopic/2352/filamentous-bacteriophage-in-bionanotechnology-bacterial-pathogenesis-and-ecology

Contacts:
A/Prof Jasna Rakonjac; j.rakonjac@massey.ac.nz
https://scholar.google.com/citations?user=N6BHLWoAAAAJ

A/Prof Andrew Sutherland-Smith; A.J.Sutherland-Smith@massey.ac.nz
https://scholar.google.com/citations?user=yHcnJ2wAAAAJ&hl=en

Massey University PhD programme:
http://www.massey.ac.nz/massey/learning/programme-course/programme.cfm?prog_id=-1005

PhD available studying co-evolutionary dynamics at the Max Planck Institute for Evolutionary Biology in Plön, Germany

We are seeking a motivated PhD student to join our research team working
on eco-evolutionary dynamics at the Max Planck Institute for Evolutionary
Biology in Plön, Germany.

We are looking for a highly motivated ecologist or evolutionary biologist
to join our group Community Dynamics at the Max Planck institute for
Evolutionary Biology (http://web.evolbio.mpg.de/comdyn) and the Kiel
Evolution Center (http://www.kec.uni-kiel.de). The ideal candidate is
fascinated by evolutionary and ecological questions, independent and
creative. She/he has a background in evolutionary biology, population
or community ecology. A MSc (or equivalent) in Biology is required.

There is a continuing interest to identify the interactions and feedback
dynamics between ecological and evolutionary changes at the same time
scale. This interest in eco-evolutionary dynamics is fuelled by the
need to understand how populations and communities could adapt to rapid
environmental change such as warming, invasion and pollution. Despite
this pressing need to understand eco-evolutionary dynamics, they are
not well understood in complex systems. In the project we aim to (1)
identify rapid adaptive changes in coevolving host-virus populations in
different food webs that differ in the types of species interactions and
complexity and to (2) comprehend how the dynamics of adaptive changes
alter the ecological dynamics and potential feedbacks. We will combine
controlled laboratory experiments, whole genome sequencing of populations
across different time points and modeling to characterize and compare
the adaptive dynamics and their consequences within the different food
webs. For more information on potential the project contact Lutz Becks
(lbecks@evolbio.mpg.de).

The institute offers a stimulating international environment and
an excellent infrastructure with access to state‐of‐the-art
techniques. The town of Plön is in the middle of the Schleswig-Holstein
lake-district within a very attractive and touristic environment near the
Baltic Sea, close to the university towns of Lübeck and Kiel. Hamburg
and Lübeck are the closest airports.

The position is funded for three years.  We ask applicants to send
a PDF file containing their CV and letter of motivation as well
as contact information of two references by e-mail to Lutz Becks
(mailto:lbecks@evolbio.mpg.de). We will begin reviewing applications
starting March 22th until the position is filled.

The Max Planck Society is an equal opportunity employer.

PhD Student Position

Monash University: Microbiology in Bacteriophage

A PhD position is available to work with Dr Jeremy J. Barr at Monash University, School of Biological Sciences, in Melbourne, Australia. We are looking for motivated, talented and enthusiastic PhD students with an interest in microbiology. With cutting-edge interdisciplinary project, excellent resources, and a strong publication focus, the Barr Lab provides an outstanding opportunity for all students. To learn more, visit thebarrlab.org

Project details:
Bacteriophage are specialist viruses that infect bacteria and are the most abundant biological entities on the planet. Within our bodies, bacteriophages control and manipulate our bacterial microbiota, prevent infection and disease and have interactions with eukaryotic cells and surfaces. Our lab has demonstrated the interactions of bacteriophage with mucus layers that provides an antimicrobial layer (Barr et al., PNAS 2013, 2015). The aim of this PhD project is to investigate the interactions of bacteriophage with bacterial hosts and eukaryotic cells using in vitro experimental systems. In doing so, you will gain expertise in microbiology, bacteriophage biology, infectious diseases, next-generation sequencing, tissue culture, microfluidics and experimental biology.

Scholarship details:
The Barr Lab has three fully-funded scholarships available for domestic and international students interested in doing a PhD. The 3.5 year award includes all course fees and a $26,000 AUD per year tax-free stipend. Additional expenses for relocation, coursework and conference attendance will also be covered.

Monash and the School of Biological Sciences:
Monash is a member of the Group of Eight, a coalition of top Australian universities recognized for their excellence in teaching and research. The School of Biological Sciences is a dynamic unit with strengths in ecology, genetics and physiology and the nexus between these disciplines (monash.edu/science/about/schools/biological-sciences/). The University is located in Melbourne, one of the most liveable cities in the world and a cultural and recreational hub.

Application process:
Interested candidates should send their CV, academic transcripts and a brief outline of research interests and motivation to jeremy.barr@monash.edu Applicants must possess a Bachelor’s or equivalent degree with first-class Honours, MSc or MPhil degree in a relevant subject (e.g., microbiology, genetics, ecology). Review of applications will begin immediately and short-listed candidates will be contacted for more information and invited to interview.