Student Projects

Introduction: Campylobacter jejuni is the major cause of food-borne bacterial diarrhea worldwide. It has long been believed that most human C. jejuni infections are sporadic and not associated with specific strains. However, by routinely applying whole genome sequencing and advanced genotyping methods, recent work has shown some C. jejuni strains dominate in Danish poultry production for years and are associated with most human cases. Yet currently we do not know how these high-impact C. jejuni strains are able to persist and how they differ genetically and phenotypically compared to low-impact C. jejuni isolates.

Aim: Identify genetic and phenotypic characteristics in high-impact C. jejuni strains by detailed bioinformatic analyses combined with high-throughput phenotypic screening assays.

Your work: You will use selected high-impact and low-impact C. jejuni isolates of chicken, food and human origin isolated by Statens Serum Institut (SSI) in recent years and use bioinformatics and wet-lab experiments to identify specific genetic and phenotypic traits associated with being high-impact. The project is a collaboration with SSI and involves a stay there to learn and perform the bioinformatic analyses. Furthermore, you will learn how to work with pathogenic bacteria and get GMOII lab experience as well as be working in international research labs.

Methods: C. jejuni cultivation experiments, comparative genomics and more detailed bioinformatic genome analyses, assist in developing high-throughput phenotypic analyses, etc.

Contact: Assistant professor Martine C. H. Sørensen mcp@sund.ku.dk

Introduction: Campylobacter jejuni is the major cause of food-borne bacterial diarrhea worldwide and the main reservoir associated with human disease is broiler chickens. C. jejuni is highly adapted and can colonize a specific niche in the chicken gut to very high numbers without causing disease in the birds. We are currently developing a chicken gut-model system allowing us to study different interventions targeting C. jejuni in the chicken reservoir such as the use of bacteriophages which are bacterial viruses that kill bacteria.

Aim: Test and evaluate bacteriophage-based products targeting C. jejuni in the chicken gut using a newly developed chicken gut model system.

Your work: You will test and evaluate bacterial reductions after the addition of a bacteriophage-based product targeting C. jejuni in our newly developed chicken gut model system. You will assess sensitivity of individual C. jejuni isolates towards the bacteriophage-based product in vitro and use whole genome sequencing to identify genetic features that may be associated with sensitivity or resistance towards the bacteriophage-based product. You will also work on optimizing the gut model system for other types of experiments. The project is a collaboration with ISI Food Protection in Aarhus and involves a stay there to learn and work with the chicken gut model system. Furthermore, you will learn how to work with pathogenic bacteria and get GMOII lab experience as well as be working in international research labs.

Methods: C. jejuni and bacteriophage experiments, work with and assist in further developing a new chicken gut system, DNA isolation, whole genome sequencing, genome sequence analyses, etc.

Contact: Assistant professor Martine C. H. Sørensen mcp@sund.ku.dk

Introduction: Campylobacter jejuni is the major cause of food-borne bacterial diarrhea worldwide. The main reservoir associated with human disease is broiler chickens as C. jejuni is highly adapted and can colonize the chicken gut to very high numbers without causing disease in the birds. Recent work has demonstrated that while some C. jejuni strains continue to exist in low numbers in the chicken gut, others can dominate and grow to very high numbers (high-impact) posing a significant risk for human health. We have recently shown that resistance to phages present in the chicken gut could be a major player in being able to efficiently colonize and outcompete other C. jejuni isolates in this niche.

Aim: Investigate phage resistance and phage resistance mechanisms of high-impact C. jejuni strains

Your work: You will use selected high-impact (dominant) and low-impact C. jejuni strains of chicken, food and human origin isolated by SSI in recent years. You will use phage-based laboratory assays in combination with bioinformatic analyses to identify if high-impact strains have competitive advantages compared to sporadic isolates related to phage resistance. Furthermore, you will learn how to work with pathogenic bacteria and get GMOII lab experience as well as be working in an international research lab. The project is a collaboration with Statens Serum Institut and will involve at stay there to learn and perform the bioinformatic analyses.

Methods: Hands-on C. jejuni and bacteriophage experiments, comparative genomics and more detailed bioinformatic genome analyses, etc.

Contact: Assistant professor Martine C. H. Sørensen mcp@sund.ku.dk

Introduction: CRISPR-Cas has been used in E. coli and other bacteria to genetically engineer bacteriophages (phages). However, such plasmid-based systems are not compatible with the major zoonotic pathogen Campylobacter jejuni. Recently, our collaborators in the UK developed a CRISPRi platform located on the bacterial chromosome of C. jejuni. However, it has not been studied if CRISPRi can be used to genetically engineer phages infecting C. jejuni.

Aim: Genetically engineer Fletchervirus phages infecting C. jejuni using CRISPRi as a proof-of-concept.

Your work: You will use CRISPRi-modified C. jejuni strains sensitive to Fletchervirus phages with guides targeting one of the receptor binding proteins (RBP2) to as a proof-of-concept show that you can modify phages using this technology. If successful, you will design and modify CRISPRi strains with new guides targeting other phage genes of interest. Furthermore, you will learn how to work with pathogenic bacteria and get GMOII lab experience as well as be working in an international research lab.

Methods: Hands-on C. jejuni and bacteriophage experiments, CRISPRi guide design and application in C. jejuni, basic molecular techniques, bioinformatic genome analysis, etc.

Contact: Assistant professor Martine C. H. Sørensen mcp@sund.ku.dk

Introduction: Flagellotropic bacteriophages (phages) are bacterial viruses that are dependent on motile flagella for successful infection of their bacterial host. This group of phages has been suggested as excellent candidates for phage therapy targeting pathogenic bacteria where flagellar motility is associated with bacterial colonization or virulence. Firehammervirus are flagellotropic phages infecting the zoonotic pathogen Campylobacter jejuni but the interaction with the bacterial host is not well studied, and it is not known how these phages recognized and bind to their bacterial host.  

Aim: Identify components of Firehammervirus important for host recognition.

Your work: You will clone, express, and purify phage components suggested to play a role in bacterial host recognition and add markers to study how and where they bind on the bacterial surface. You will also apply phenotypic assays in combination with phage antibodies to verify functions, genome sequence analyses to predict new functions and transmission electron microscopy to study the phage-host interaction. Furthermore, you will learn how to work with pathogenic bacteria and get GMOII lab experience as well as be working in an international research lab.

Methods: Hands on C. jejuni and phage experiments, cloning, protein expression and purification, bioinformatic genome analyses, transmission electron microscopy, etc.

Contact: Assistant professor Martine C. H. Sørensen mcp@sund.ku.dk

Introduction: E. coli is a highly diverse bacterium that may be a harmless commensal or a serious pathogen, causing a long range of infections. Its large diversity is resembled in the E. coli reference collection (ECOR).  Due to the rising threat of antibiotic resistant bacteria, phage therapy targeting certain E. coli strains might be an important strategy. To efficiently use phages against pathogenic bacteria, it is essential to understand how phages bind and infect their host as well as how they can overcome bacterial defense mechanisms. By characterizing a small but diverse E. coli phage collection, it is possible to investigate phage binding and infection and identify novel phage resistance mechanisms in E. coli using the ECOR collection.  

Aim: Characterize host range and receptor usage of an E. coli phage collection and identifying potential new phage resistance mechanisms in E. coli.

Your work: By characterizing an E. coli phage collection, you will learn how to work with phages and its bacterial host. Using microbiological methods, you will analyze the phages’ host range and receptor usage. You will also use bioinformatical and molecular methods to identify the bacterial resistance mechanisms and use cloning strategies to engineer phages to expand their host range. Furthermore, you will gain experience in working in a GMOII lab as well as an international research group.

Methods: E. coli cultivation and phage propagation, phage host range determination, different bioinformatic tools to analyze bacterial genomes, molecular cloning

Contact: Professor Lone Brøndsted, lobr@sund.ku.dk