The Edwards lab at Flinders Uni always has several open PhD projects, and if you are interested you should contact Rob. These projects are available at the start of 2022, so if you find this page and it’s no longer 2022, you should definitely contact Rob, because someone will have done something amazing with these projects (but perhaps not the projects themselves)!
Some of the projects have funding available, but funding will be dependent on your background, research experience, grades in other classes. In addition, there are several scholarships, including scholarships just for PhD students, you can (and should!) apply for.
Note that we have broken these out into experimental and computational projects, but in reality, everyone in our lab does both. Some people do more of one than the other, but we are an interdisciplinary group, and we all try to be experts at everything!
There is always room for you to learn how to do experiments or how to write code.
Also, these descriptions are deliberately brief. If you end up doing what you started out thinking you were going to, then you probably haven’t grown as a scientist and been challenged with new ideas. These are general directions we want to head (like “let’s go north”) not turn-by-turn directions on how to get to the end of your project. There is lots of room to adapt and experiment.
Counting microbes in complex samples
Sounds easy, right? Count some microbes in an environment. What about counting all the microbes in an environment? Of course, the great plate count anomaly suggests that we can’t count them all. We are going to develop a flow-cytometry based assay to count all the cells in the environment, using spike-ins and controls. We want to try a range of different cell shapes, sizes, morphologies, to see how our detection varies. In this PhD you will design the probes and run the experiments to count all the bacteria in different environments. Of course, we’ll add some metagenomic sequencing and bioinformatics analysis to challenge you.
Design Probes for Clades of Bacteria
We’ve used the 16S sequence primers because they work for all bacteria, but what if we could identify probes for specific clades of bacteria. We can do that computationally, why not experimentally? For this PhD you will start with by using the complete genomes from PATRIC (don’t worry – we already have them) and identify all 20-mers in the DNA sequences (there are ~1012 possible 20-mers so it is easier to count those that are present rather than eliminate the possible 20-mers that are absent). Then let’s eliminate those with very low or very high Tm and those likely to self-anneal, and identify all of those that match specific clades. Then you’ll get to work testing them in our new experimental systems.
You will compare the quantification of microbes by your clade-specific probes to the traditional rank abundance curves to see how well (or poorly) the rank abundance curves represent the population. The discordance between the number of DNA sequence reads in a metagenome and the number of microbes counted will allow you to identify groups of microbes that are being under- or over-reported by traditional metagenomics approaches and design approaches specifically to target those microbes.
Take the “relative” out of relative abundances
All metagenomic approaches at the moment use relative abundance: rank abundance curves, and their abstractions as diversity measures, are the most widely used microbiome statistics, and yet they are currently not based on actual microbial counts. During your PhD you will calibrate rank-abundance curves by comparing the number of microbes to the proportion of DNA sequences recovered. You will develop calibration curves for groups of microbes that are expected to behave similarly (e.g. all Mycobacteria are expected to have similar DNA extraction and sequencing efficiencies, but you will test this with our unique experimental approaches). This will be the first truly quantitative application of metagenomics to an environmental sample!
Phage Isolation for Phage Therapy
Like many labs around the world, we are heading the call to phage therapy. We are isolating phages against a range of pathogens from a variety of sources. For this project, you will need to isolate and characterize phages to selected pathogens (as discussed with Rob). The purification will include making sure the phages are pure enough to be given to a patient, DNA sequencing and bioinformatics analysis to ensure that the phages do not have any “bad” genes that might adversely affect the patients and electron microscopy characterization of those phages. There is also some computational development required (see the computational section) to identify different phage genes.
New software to combine flow-cytometry and metagenomics
In this computational PhD you will develop computational tools that will allow the correction of rank-abundance curves based on flow cytometry data. This will enable any biologist to collect a sample, set a portion aside for flow cytometry while the virome or metagenome is being sequenced, and to normalize their metagenomes based on the actual number of microbes in their sample. Furthermore, you will adapt metagenome-assembled genome binning approaches to be informed by the actual number of each microbe present in the sample.
Probabilistic Protein Annotations
More than 2/3 of the phage proteins are called “hypothetical proteins” … in other words, we don’t know what they do. Let’s see if we can come up with some new ideas. For your PhD, you will design new tools for genome annotation using models of phages incorporating synteny. Your model will start from an annotated genome and identify the most probable gene function! Your code will read a GenBank format file or a similar file and assign a function and a likelihood that the function is correct for each of the reading frames in that file. You are going to need to develop a data structure to hold the results, and then build a web-based interface to query your database.
Expand Phage Taxonomy
Over the years, we have developed a few tools and ideas about phage taxonomy, and it’s time to revitalize that approach. In your PhD, you will develop a new approach to identify phage taxonomy and assign phages to a specific taxonomic group. Your amazing website will allow users to select appropriate branches of the taxonomic tree and identify biomarkers that are specific to that branch. We want to make it interactive and allow both upload and download of data, as well as back-end code that creates taxonomic groupings.