PhD student in In Vitro Diagnostics, CRISPR–Cas / Electrochemistry

Dr Daniel A. Richards and Professor Andrew J. deMello, in the Institute for Chemical and Bioengineering at ETH Zürich (ETHZ), and Dr Loïc Burr of the Swiss Center for Electronics and Microtechnology (CSEM), are searching for a PhD student to develop CRISPR–Cas-based electrochemical biosensors for multidrug resistant Mycobacterium tuberculosis (MDR-MTB). This work is funded as part of a SNSF BRIDGE Discovery grant, and you would work as part of a multiinstitutional consortium, including ETHZ, CSEM, the Swiss Tropical Public Health Institute (Swiss TPH), and the National Centre for Tuberculosis and Lung Disease (NCTLD) in Tblisi, Georgia. The position will ideally be filled by someone with a background in CRISPR–Cas and/or electrochemical biosensing, though anyone with experience in biosensing or analytical chemistry will be considered. This is a four-year position, and will include time at both ETHZ and CSEM.

Tuberculosis (TB) kills an estimated 1.25 million people each year, making it the single deadliest infectious disease. Unfortunately, TB disproportionately impacts low- and middle-income countries (LMICs); 98% of the global TB cases occur within LMICs, leading to devastating effects. Furthermore, the proliferation of this disease has resulted in widespread misuse of antibiotics, leading to the development of substantial drug resistance. Indeed, in the worst-affected regions, drug resistance among recurring TB infections has risen above 50%.

Most TB deaths are preventable if diagnosed early. However, almost a quarter of all TB cases go undiagnosed. Similarly, the proliferation of drug resistance in TB can be partially attributed to a scarcity of effective methods for identifying resistance markers, which results in poor antibiotic stewardship. Unfortunately, contemporary diagnostic technologies have proved insufficient for diagnosing TB and associated drug resistances, particularly at the point-of-care (PoC). Few technologies exist that can quickly and accurately diagnose TB and simultaneously determine resistances, and those that can are large and expensive, precluding their use in LMICs. They are also overly reliant on sputum samples, which can be difficult to obtain, particularly in low-resource settings.

In this PhD project, we aim to develop RPA–CRISPR–Cas assays capable of multiplexing 14 targets for TB and associated markers of drug resistance from a single sample. These assays will be combined with novel electrochemical reporters to facilitate miniaturization and provide quantitative readouts of disease. To facilitate deployment at the PoC, we will leverage the facilities and expertise of CSEM to integrate these technologies into a highly affordable cartridge & reader system. The research team will be supported by the Swiss Tropical and Public Health Institute and the National Center for Tuberculosis and Lung Disease in Georgia, who will validate the technology in patient samples and perform a small pilot study. This will provide the student with the opportunity to travel and perform fieldwork.

These assays will fill a critical gap in the current treatment pathway of TB and bring care to millions of underserved patients, particularly in LMICs. By enabling rapid diagnosis of TB, this technology will facilitate more accurate and timely medical interventions, ultimately improving patient outcomes and decreasing the burdens on healthcare systems. Moreover, by focusing on common drug resistance markers, this technology will improve antimicrobial stewardship and be a valuable weapon in the fight against antimicrobial resistance (AMR).

Job description

Profile

• A multicultural and multidisciplinary research environment
• Attractive hiring conditions
• Access to state of the art equipment and resources
• Strong support in career progression