This phase I project scope is to develop the PTMsenseTM , a novel microscale electrochemical biosensor for highly sensitive detection of protein modifications. The biosensor will be further integrated (outside the scope of the phase I project) as the core technology of companion diagnostic kits that will allow matching a drug to a cancer patient in point-of-care settings.

Shift to personalised medicine

Today, medical practice is mostly based on a trial and error approach for treatment selection, often resulting in loss of critical time and unnecessary exposure to toxic drugs. Due to suboptimal outcome, the face of medical practice is undergoing a profound change by adopting personalised medicine as an emerging approach for disease management and patient care. Personalised medicine takes into account individual variability based on molecular biomarkers to determine which medical treatment will work best for each patient. This is especially critical in cancer where the overall percentage of responders to available drugs is <50% and even the newest drugs do not benefit the majority of patients.

The most indicative biomarkers are proteins whose function controls the actual physiological state Proteins are responsible for carrying out all biological processes and their activity is the ultimate determinant of physiological state of cells and tissues. Protein activity and function are controlled by a set of chemical modifications that occur after a protein is produced, termed Post-Translational Modifications (PTM). These modifications determine whether a protein will be active or not, where it will reside in the cell, and when it will be sent for disposal.

Specifically, modification by ubiquitin is involved in different aspects of the tumorigenic process of cancer development and progression, such as dysregulation of cell growth and resistance to apoptosis.

Project aim

PTM Biosciences is dedicated to advancing personalised medicine by transforming Post-Translational-Modifications into novel biomarkers for disease management. Prof. Lital Alfonta at the Ben-Gurion University specialises in bioelectrochemistry and in genetic code expansion, which enables the incorporation of non-canonical amino acids (ncAAs) into proteins. The project partners have identified PTM-based molecular signatures of cancer patients associated with response to different therapies. The partners will combine their complementary knowledge and technology to develop a portable, miniaturised  electrochemical biosensor for highly sensitive detection of protein modifications by ubiquitin in clinical samples. In a later phase outside the scope of this project, the biosensor will be further integrated as part of a point-of-care companion diagnostic kit that will allow, in a fast and accessible way, the prediction of patient sensitivity to a certain treatment, and the optimisation of therapy route, thus facilitating personalised medicine and improving the clinical outcome of cancer patients.