Master thesis projects in the field of Proteomics
Proteomics tools as antibodies and technological platforms are being increasingly used for analysis of body fluids aiming to identify biomarkers for diagnosis, prognosis, or surveillance of most common disorders. This is crucial for Duchenne and Becker Muscular Dystrophy, two rare disorders that affect only boys with short life expectancy.
Two master thesis projects are available in the field of antibody-based proteomics (1) validation of biomarkers in large longitudinal cohorts and (2) development of immunoassays for selected biomarkers. The projects are done in collaboration with Leiden University Medical Center, Newcastle University and University College of London.
Oligonucleotide mediated detection to increase the sensitivity of biomarker quantification methods
KTH - CAVIDI collaborative master project
Proteomics tools as antibodies and protein quantification platforms are being increasingly used for analysis of body fluids aiming to identify biomarkers for diagnosis, prognosis, or surveillance of the most common disorders. This is also crucial for a range of incurable muscular dystrophies like Duchenne, Becker Muscular Dystrophy, Limb-Girdle, Faciosacapulohumeral dystrophy and others. Patients suffer from progressive muscle weakness that leads to loss of walking ability and if untreated has fatal consequences for the patient.
Serum is a complex mixture of proteins, metabolites, hormones, etc. with concentration dynamic range that vary over several orders of magnitude making it challenging to quantify low-abundant proteins. Detection and quantification of protein biomarkers is therefore dependent on the limit of detection. The sensitivity of protein quantification methods impacts discovery of biomarkers, thus favoring identification of more abundant biomarkers at the expense of less abundant biomarkers. Currently detection of biomarkers in serum or plasma using bead based immunoassay utilizes biotinylation of blood proteins through non-specific conjugation of N -hydroxysuccinimide ester (NHS)-biotin to random lysine residues as a single pre-treatment step before streptavidin-R-Phycoerythrin is used for detection. The aim of this project is to explore if the biomarker detection sensitivity using the suspension bead array can be improved by replacing the biotin mediated detection with an oligonucleotide mediated detection based on BOLD binding-oligo-ladder-detection. To integrate the current immunoassay with BOLD, click chemistry and other methodologies will be used to label proteins and antibodies with oligonucleotides and detector molecules (Phycoerythrin). These approaches will be tested to potentially enhance the sensitivity of the immunoassays and lower the limit of detection.
The project will be performed at KTH, the AlbaNova campus, and at CAVIDI ( https://cavidi.se/about-cavidi/ and https://cavidi.se/exazym-kits/).
Questions and applications are sent to Cristina Al-Khalili Szigyarto at: caks@kth.se
