Biomotif is the coordinator of a new Eurostars funded project that will commence on February 25 2019.
AD Scanner – a Novel Device for Prognosis of Alzheimer’s Disease by Fast and Simple Blood Analysis
We have recently discovered that protein concentration in the isoelectric point (pI) range of pI=7.35±0.05 is much higher in blood of Alzheimer's disease (AD) patients that will later rapidly lose their mental abilities (“fast decliners”) compared to those who will slowly decline mentally (“slow decliners”). To capitalize on this groundbreaking discovery that was done using our “pI-Trap”, we will fundamentally rebuild that instrument into a novel AD Scanner, optimized to isolate and measure the protein concentration in that narrow pI range in a fully automated, unattended around-the-clock operation. The analysis of patient’s blood with an AD Scanner will be fast and inexpensive, and will be able to predict with high certainty the rate of mental decline in a given patient. The analysis is non-destructive, and the analyzed fractionated blood can be collected after passing through the instrument for further analysis. In this project, we will create the AD Scanner, test it on novel cohorts of AD patients, and commercialize it for both clinics and academia.
One of the major challenges of modern medicine is to understand how the human organism functions defending itself against invasions and diseases. The biggest mystery is the human immune system, understanding which ultimately requires knowledge of the sequence repertoire of human antibodies. The purpose of the TopSpec project is to be the first in the world aiming to solve this challenge, opening up opportunities in medical research and drug development that are today only dreamt about. We will create a breakthrough technology that will revolutionize academic, clinical and industrial proteomics and dramatically advance the development of new generation antibody- and protein-based therapeutics.
Antibodies represent the most sophisticated line of natural defense against disease. Knowing exactly which antibodies are produced in response to a particular disease enables us not only to better understand the cause of the disease but also to provide new-generation cures in the form of personalized therapeutic antibodies. The limiting factor for this to truly be achieved is to find a way to analyze and sequence large molecules in the gas phase, and this represents a formidable challenge.
The TopSpec project will develop ground-breaking TOP-down tandem mass SPECtrometry (MS/MS) approaches based on novel radical gas-phase ion-electron and ion-atom reactions, and implement them on a unique, hyphenated, ultrahigh-resolution MS platform. Another “killer innovation” is the ability to greatly simplify MS/MS spectra of large molecules by adding another dimension of separation – collisional cross-sections of fragment ions – without additional hardware and thus without sensitivity losses typical for ion mobility set-ups. Instead, the decay constants of individual isotopic peaks of fragment ions will be determined from the transient in Fourier transform MS (FT MS), and then clustered together into individual isotopic distributions. While the idea of using transient decay constant as a proxy for collisional cross sections is not new per se, TopSpec will be the first project to implement it for deconvolution of massively overlapping isotopic clusters, solving one of the greatest challenges in top-down MS of large molecules.
In the project, key experts in radical-assisted sequencing of proteins team up with best developers in ultrahigh-resolution MS and tandem MS instrumentation as well as top European scientists in MS data processing and online protein separation. Achieving the impossible, we plan to create, test and validate a seamless platform through design of sophisticated integrative software, novel methodology and analytical approaches which capitalize on our ground-breaking innovations. The resulting technology will, for the first time, enable scientists from academia and industry alike, to explore antibody repertoire by whole protein sequence analysis, enhancing the ability of the scientific world to explore new effective cures for major global diseases, such arthritis, Alzheimer’s disease and cancer, with the enhanced potential to develop new therapeutic molecules and treatments.