Li Honours Projects

Dr Simone Li
Microbiome Systems
Department of Microbiology
Monash Biomedicine Discovery Institute
simone.li@monash.edu

Microbiome Systems Lab
We are a new research group in the Biomedicine Discovery Institute, with an interest in creating multi-disciplinary, data-oriented approaches to study and compare the evolution of microbial communities in natural environments, such as soil and the human gut microbiome.

New developments in DNA sequencing technologies have advanced the field of metagenomics, enabling the genomes of different microbes in a single ecosystem to be analysed simultaneously. This has revealed, for example, an intriguing dual role of the microbiome in maintaining homeostasis as well as disrupting health.

Our recent work on the gut microbiome revealed ecological patterns of engraftment in faecal microbiota transplantation (FMT) patients undergoing treatment for different diseases (Science 2016, Nature Medicine 2022). Here, we developed new computational methods and tools to accurately profile the 1000s of microbial species in the human gastrointestinal tract and identify and track donor strains over time (Genome Biology 2015, Bioinformatics 2016, Nucleic Acids Research 2017, eLife 2019). By integrating our results with clinical metadata, we discovered certain bacteria that are more likely to persist in patients and identified aspects of the medical procedure that would facilitate this phenomenon. These findings transformed our understanding of how FMT works and its lasting impact on the microbes in our gut. It also motivated the use of precision medicine approaches to increase the success of therapies that target the microbiome - a growing global market that is estimated to reach >US$1.5bil by 2027 (BCC Research, Feb 23).

By unravelling the complex layers of biology contained within the microbiome in its native context, we aim to discover new approaches to prevent and treat disease, and introduce ways to improve and enhance current practices in clinical, biotechnology and environmental bioremediation settings.

We use advanced bioinformatics, machine learning and high-performance computing to test our biological hypotheses on new and existing data, generated by both established and emerging -omics technologies. Our team collaborates with experts around the world to develop, contextualise and build the biological picture around our findings and further our impact.

We are a growing lab and while our research is primarily data-driven, keen students with a good grasp of microbiology and genome analysis are welcome and encouraged to get in touch.

Projects

Antimicrobial resistance in the human microbiome: transmission and persistence

Background: Antimicrobial resistance (AMR) is a one of the greatest threats to human health and recognised by the World Health Organisation as a Global Health Challenge. There is an urgent need for new ways to stop its emergence, transmission and persistence. This is especially critical in clinical settings, where patient recovery is often complicated by acute and chronic drug-resistant infections caused by pathogens of unknown origin.

Project Aims: In this project, you will leverage metagenomic and clinical data to monitor and track AMR microbes in the microbiomes of various body sites. Do the same microbes that thrive in our gut also persist on our skin? Does this change when we get sick, and what other factors promote the spread of AMR in the microbiome?

Techniques: This is a dry lab project. Students will develop data skills in AMR research, metagenomics analysis and computational microbiology in this project that could drive the design of more targeted therapeutics to prevent the spread of antimicrobial resistance.

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Large-scale comparative genomics of S. aureus isolates from post-surgery patients

Background: Patients are often prescribed antibiotics immediately after surgery to prevent and control infection. There are ongoing efforts to optimise this treatment, and avoid inadvertently creating conditions that favour the growth and persistence of superbugs such as methicillin-resistant Staphylococcus aureus (MRSA).

Project Aims: In this project, you will analyse and compare 100s of S. aureus genomes and AMR profiles. These represent DNA-sequenced isolates that we collected from patients who received antibiotic treatment after surgery, in a recent clinical trial led by Prof Trisha Peel (Dept of Infectious Diseases, Alfred Hospital & Monash Uni).

Techniques: This is a dry lab project. Students will gain experience in advanced bioinformatics and microbial genomics as well as unique insights into clinical science in this project that bridges antimicrobial stewardship, computational microbiology and infection prevention.

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Faecal microbiota transplantation: how does it work and is it safe for your microbiome?

Background: Faecal microbiota transplantation (FMT) involves the transfer of gut microbes from (the stool of a) healthy donor to patient. The medical procedure is well-known for its high success rates in treating recurrent C.difficile infection and has become a potential therapeutic option for an increasing number of chronic diseases. However, we still don't know how it works and there exists a risk of undesired side effects. For example, severe infections and other diseases have been described in some patients soon after they received FMT treatment for unrelated illnesses – whether this was pure coincidence or caused by FMT is unclear.

Project Aims: In this project, we will study genomic diversity in the gut microbiome of FMT patients and their donors. What could drive a successful FMT? Can we design a safer treatment for patients with chronic conditions with no alternative treatment?

Techniques: This is a dry lab project. Students can tackle these questions or pursue their own, gaining experience in data science, statistics and comparative metagenomics in this exciting project at the nexus of discovery and clinical sciences.

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Where on Earth are carbon-fixing microbes?

Background: CO2 is being produced faster than the rate we can remove them from the biosphere. There is a global need for new solutions to augment carbon fixation processes that already exist in nature. Recent studies suggest that microbes from a diverse range of environments could possess undiscovered mechanisms to convert CO2 – but we don’t know where to find them.

Project Aims: In this project, we will study 1000s of microbes captured in metagenomes from samples collected around the world to identify hotspots of carbon-fixing microbes. Are they enriched in certain geographies or ecosystems? Where could we potentially discover new microbial CO2 conversion pathways?

Techniques: This is a dry-lab project. Students will be able to apply their genomics skills and molecular biology knowledge while gaining experience in integrating and analysing large biological datasets in this international collaboration project.

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