Project Title: Engineering fluorogenic antibodies for 1-step reagentless biosensors

Supervision: The project will be co-supervised with protein engineering and disease experts at the Victorian Heart Institute and/or the Monash Centre to Impact Antimicrobial Resistance.

Project Overview:

The detection and quantification of proteins in complex biological samples has traditionally been based on time-consuming and multi-step ELISA (Enzyme-Linked Immunosorbent Assay) procedures. Currently, ELISA procedures range from manual procedures through to automated lab-based procedures and even “point-of-care” handheld systems, however the fundamental need for multiple assay steps and reagents still applies. De-centralisation of laboratory assays from tertiary hospital and pathology labs to local health centres, ambulances, GP clinics and in the home, requires innovative new technologies to simplify assays without compromising on critical parameters (specificity, sensitivity, etc).

NEL has recently generated a new platform of engineered antibodies which are designed to capture target proteins from complex mixtures and to simultaneously report the binding event as detectable changes in fluorescence spectra. With the basic mechanism described recently, we are now looking to incorporate these sensors into in vitro or in vivo diagnostics. Key goals include producing engineered antibodies that generate fluorescence changes in response to targets when bound to surfaces, broadening out the range of optically-active reporters that can be incorporated into the antibodies, and deploying these sensors in human clinical samples (for in vitro diagnostics applications) or in animal models of disease (for real-time, in vivo biosensing).

Student Background/Experience: In this Project, students will spend the majority of their time designing, engineering, expressing and evaluating antibody-based sensors. It will be an interdisciplinary project, working with engineers, chemists, biomedical scientists and clinicians. Those students with academic backgrounds in engineering and/or science, with experience in molecular biology, are encouraged to apply.

Project Title: Rapid, scalable and sensitive in vitro diagnostic immunoassays using biological agglutination phenomena

Supervision: The project will be co-supervised with IVD experts in the Chemical Engineering Department and commercial partners.

Project Overview:

COVID-19 has caused a worldwide viral pandemic, with >500,000 deaths and >10,000,000 cases reported internationally (June 2020). Large-scale efforts are underway to develop vaccines and anti-viral drugs, and epidemiological methods of social distancing and quarantine are being used to reduce the spread of infection. While PCR tests are broadly available to confirm current cases of COVID-19 infection, there is currently a lack of high-throughput, lab-based screening tests that detect viral antigens during infection, or the antibody response following viral infection. Point-of-care paper-based tests for antibodies are emerging, but they cannot be used for high-throughput screening, and results will need to be confirmed in high specificity/sensitivity lab tests.

NEL researchers, in collaboration with Monash ChemE groups led by Prof Gil Garnier, Prof Mark Banaszak Holl and A/Prof Tim Scott, recently developed SARS-CoV-2 antibody tests using widely available blood typing technology. The reagents and consumables for these tests are already produced at scale, and we are currently in negotiations with companies to roll out the assay across the country and beyond. However, it is clear that this robust platform can be employed to rapidly develop new assays for other disease biomarkers, easily fitting into existing clinical workflows.

Student Background/Experience: In this Project, students will spend the majority of their time designing unique agglutination assays and required reagents (e.g. engineered peptides, proteins, antibodies, nanoparticles and combinations thereof), and will work in an interdisciplinary team on a milestone-based program. Students with a background in engineering, with additional training in science and/or experience in lab work are encouraged to apply.

Project Title: Combining nanosensors with biomedical imaging approaches to create novel, real-time and continuous in vivo biosensors.

Supervision: The project will be co-supervised with experts at the Monash Institute for Pharmaceutical Sciences, disease experts in Melbourne and commercial partners.

Project Overview:

In vivo biosensing is a “blue-sky” research area in the group, where our goal is to monitor the concentrations of key disease-related biomarkers inside living animals and humans, in a real-time and continuous manner. Aside from the advantages that these sensors could provide in terms of understanding inherently dynamic biological processes in vivo, there is a myriad of clinical conditions that are characterised by rapidly deteriorating processes for which continuous monitoring applications would dramatically change treatment protocols (e.g. cytokine and acute phase responders in the context of sepsis; cardiac proteins in the context of heart attack).

In order to address this challenge, NEL researchers have designed nanoparticle-based sensors (“nanosensors”) paired with complementary biomedical imaging modalities (e.g. ultrasound, photoacoustics, fluorescence, MRI), evaluating their biosensing potential in live animal models. In this project, we plan to progress these biosensor strategies, launching into new disease models and targeting new analytes, using the latest advances in nanoparticle engineering.

Student Background/Experience: In this Project, students will work in an interdisciplinary team, synthesising nanoparticles and then undertaking pre-clinical animal experiments and developing novel biomedical imaging procedures. Students with a background in engineering, with additional training in science and/or experience in lab work are encouraged to apply.

Blood tests and other common diagnostic assays are designed to measure the concentration of a disease biomarker at a single moment in time. However we know that diseases are highly dynamic processes, as are our body's responses to disease and therapeutic intervention. Therefore, our long-term aim is to design nanosensors that can be introduced into the body to monitor the dynamics of the disease, the host response, and the response to therapy in situ. The only successful example of a commercialised technology in this space to date is continuous glucose monitoring - a life-saving technology for diabetics. However, translation of this approach to detect other analytes has not been successful, so we must design novel approaches for other metabolites, proteins, microbes, etc. The most compelling areas ripe for continuous monitoring include therapeutic drug monitoring, early detection of sepsis, early detection of heart attack or failure, and monitoring the response of cancers to specific treatments. This project requires a detailed understanding of how to design biocompatible devices suitable for in vivo use, how to design sensor chemistries for different molecules, and also how to detect and transduce the information. We look forward to recruiting a range of scientists (chemistry, biochemistry, biomedical science, physics, materials science) and engineers (chemical, materials, bio, electrical) to join our team and help pioneer the next generation of in vivo sensors.

PhD and Honours projects currently available include:

• Design, synthesis, characterisation and pre-clinical evaluation of nanoparticle scaffolds for in vivo sensing using a range of biomedical imaging modalities (optical imaging, ultrasound, photoacoustics)
• Structure-based and/or rational design of novel binders (enzymes, antibody scaffolds, aptamers, etc) for protein biosensing

with the following applications:

• Rapid detection of bloodstream infections in high risk patients
• Rapid detection of heart attack and heart failure
• Monitoring response to treatment and disease recurrence in cancer patients
• Monitoring the health and viability of cells grown in 3D scaffolds for tissue engineering or cellular therapies