A new method for analysing complex biotherapeutics
While mass spectrometry is an efficient and state-of-the-art method for analysing the composition of material samples and identifying the molecular content, it is not a perfect method for analysing very complex molecules and their interactions with receptors.
Victor Cheng Yin’s new project, DeMIST: Deciphering Biomacromolecular Heterogeneity by Single Molecule Mass Spectrometry, will aim at creating a new solution for this, a project that has received 17.7 mill DKK from ERC as an ERC Starting Grant.
Modern biotherapeutics, such as the mRNA vaccines, are much more complicated molecules than older types of drugs like paracetamol or insulin. Being more complex, the behaviour and structure of molecules like mRNA are also harder to understand and more difficult to analyse with existing methods. “As scientists, we don’t have the tools to understand them yet, so they are often described as “fuzzy”, partly because we don’t have the analytical tools and methods to characterize them” Victor Cheng Yin says.
Trapping and analysing complicated macromolecules
As an analytical chemist, he will develop these new tools within the field of mass spectrometry. The project will develop new single molecule methods and equipment that will make it possible to trap and analyse individual macromolecules and gain a new understanding of them and their complex interactions. Today, there are specific aspects of analysing macromolecules that mass spectrometry is not capable of when analysing the extremely complex macromolecules.
Victor explains: “Traditional mass spectrometry performs very poorly for complex macromolecules – the data we get is way too complicated for scientists to confidently interpret because there are just way too many different signals all at once. The “breakthrough innovation” with my project is that instead of looking at all the molecules at once, we look at and manipulate trapped macromolecular complexes one at a time (i.e. single molecule mass spectrometry). This is technologically much harder to do, but it lets us interpret confidently what signals are coming from what so we can begin to understand the composition of these systems”.
When developed, the new method could give researchers a deeper insight into modern vaccines, how complex macromolecules and ligands interact with the corresponding receptors, future drug development and potentially also be applicable widely for material sciences.
Two PhD’s and one post doc will be hired for the project.