When size matters: a platform to study molecular interactions and multimerisation

We are requesting funding for a system that offers a choice
of resolving the samples according to hydrodynamic volume
using either size-exclusion chromatography or field-flow
fractionation with an online multi-detector system including
multi-angle light scattering, dynamic light scattering, UVvisible
light absorption, refractometry, and the detection of
fluorescence spectra. The requested instrument allows to
separate a complex molecular sample according to the size
of the comprising molecules, followed by immediate inline
characterisation of the molecular weight, shape,
concentration and binding to conformation-sensitive dyes.
Such a setup is extremely powerful to analyse biomolecular
interactions between proteins/nucleic acids/lipids,
conformational changes (e.g. open/closed conformations of
proteins), as well as aggregation and amyloid formation and
the impact of mutations and physicochemical parameters
on all of the above.
There is broad interest in the instrument already (the
consortium submitting this application consists of ten
principal investigators and two innovation managers from
two KUL campuses), and the circle of users is expected to
widen since the instrument is very versatile and
oligomerization, conformational changes, the formation of
protein complexes and aggregation (functional or
pathologic) are common events in cells and prime targets for therapeutic intervention.