Microbial cell factories: evaluating bacteria used in biotechnologies for metabolic efficiency and genome integrity

Microbial cell factories: evaluating bacteria used in biotechnologies for metabolic efficiency and genome integrity

Supervisor: Dr Jillian Couto

School: Engineering

Description: Our modern world faces a number of grand challenges in healthcare, energy, and the environment, all of which require radical solutions.  These solutions will only come about by bridging fields of study that were traditionally thought of as separate.  An emerging epicentre of innovation is environmental biotechnology, where we are fusing the field of molecular biology with environmental engineering to design and deliver transformative solutions such as cleaner, more sustainable energy, superior in situ sensors, and state-of-the art biomaterials.  This is done by designing and manipulating new genes, sometimes known as bio-parts, and incorporating them as genetic circuits into the existing genetic material (genome) of high-performing microorganisms (bacteria).  There are a number of industrially relevant bacteria strains that are considered stalwarts of the biotechnology industries.  They have been engineered for the lab environment and so their performance levels and error-rates are well known, making them part of established protocols that make standardized products.  However, these standard strains have proved unsuitable for these new and emerging biotechnologies.  This is because biotechnologies, like any other process, can undergo a number of stresses during a production run, which appear to be exacerbated by these new and emerging products.

In response, efficient strains are now being developed, called ‘chassis’. A fundamental idea behind the chassis stems from studying bacteria and their genomes in nature.  Here, bacteria with streamlined genomes appear to thrive in certain environments.  It is thought that this reduction in genetic material leads to a more efficient metabolism for the organism.  Therefore, chassis with reduced genomes have been produced for biotechnology applications in the hopes of retaining stability throughout the process.  Chassis have now been developed for most species of lab bacteria.  Engineered bio-parts and gene circuits are also under production, ready to be inserted into these chassis organisms.  However no one has investigated how these new strains will perform if exposed to stresses that are common during these biotechnology applications. We have designed a lab-scale system to place the chassis under these stresses for a sustained amount of time, and test chassis performance.  Performance is measured by assessing genome integrity and growth efficiency of the chassis.

The prospective student will be based in the Environmental Biotechnology lab and utilize this system to test the effects of fluctuations in pH and temperature on chassis stability.  The overarching goal of the project is to accelerate the success of these emerging biotechnologies by utilizing these data to build better predictive models of these processes.

Overview of training provided:  The protocols for the work have already been established and will soon be published (Couto et al., in review; Yuan et al, in review) which will enable the student to ‘hit the ground running’.  Consumables will be covered by the Frontiers in Engineering grant.  The student will receive a lab-safety induction and training in all the relevant project-related techniques. The student will work together with the supervisor or with a technician (who is familiar with this project), on generating the data.  Lastly, the student will be encouraged to present their work at the Water and Environmental Engineering seminar series and will appear as an author on conference abstracts and publications that arise from this work.