Mass spectrometry and proteomics
Mass spectrometry is an extremely sensitive method to determine the structure of molecules, principally proteins, and to quantify them.
When directly coupled to nanoflow high performance liquid chromatography separation technology (HPLC), the mass spectrometer can identify, sequence and quantify thousands of peptides in a single experiment.
We can apply the approach to very detailed analyses of single proteins.
We can also apply the approach to produce information on all the proteins in a complex mixture, which is what we call proteomics.
We use innovative mass spectrometric and proteomic approaches to achieve the aims of NIBSC, which is improved quality control and safer medicines through better characterisation, understanding and standardisation of biological products.
We use in-depth knowledge and skills to identify areas and suitable technical approaches where mass spectrometry and proteomics can be beneficial.We undertake research and development projects to improve the characterisation of a wide range of biological products. This work involves:
- identifying and quantifying key antigens in complex vaccines, such as that against Group B meningococcal disease, to understand how changes in production strains and growth conditions affect the protein composition and immune response
- identifying total protein content of various gene therapy products to facilitate further studies to improve purification and production
- establishing complete profiles of antigens in ‘good’ and ‘bad’ batches of the vaccines, to support novel quality control approaches and support future pharmacovigilance studies
We use quantitative proteomic analyses and bioinformatics approaches to simultaneously quantify changes in the content of thousands of proteins in a cell, for example human pluripotent stem-cell-derived cardiomycytes and neuronal cells when treated with different drugs or toxins. Combining this with bioinformatics software, we identify changes in the various metabolic and biosynthetic pathways in the cell.
We develop the use of mass spectrometry for novel batch release tests, such as the absolute quantitation of key antigen(s) in complex vaccine products.
We use a combination of mass spectrometric methods to characterise potentially falsified medicines.
We also use mass spectrometry to improve the standardisation of biopharmaceuticals.
The technologies we use are:
- multi-dimensional liquid chromatography with different separation strategies
- multiplex stable isotopic labelling
- tandem mass spectrometry with various fragmentation technologies
- isotope dilution tandem mass spectrometry – multiple reaction monitoring