Two-dimensional time-domain vibrational spectroscopy for structural biology
financed by European Innovation Council and Kempestiftelserna.
This project aims to develop a two-dimensional infrared time-domain spectroscopy setup for the detection of vibrational signatures of organic molecular systems, to enable non-invasive optical recognition of molecular structural changes with an extreme spectral, spatial and temporal resolution.
Biomolecules "speak and understand" the natural language of biological processes as they occur in cells and organisms. An outstanding challenge is not only to determine the structure, but indeed understanding the function of fundamental biological entities, such as proteins, whose dimensions are below the diffraction limit of light (few nanometers).
Progresses towards non-invasive biomolecular specificity via detection of vibrational signatures and their correlations at very high spectral and temporal resolution, have been brought by the development of two-dimensional mid-infrared (2D-MIR) time domain spectroscopy (TDS). Although measuring correlations between coherent vibrations in organic molecular systems is technically challenging, it could bring the highest degree of biomolecular specificity.
In this project, we will develop an ultrafast coherent 2D-MIR TDS setup to detect vibrational signatures of molecular systems, thus helping to recognize structural changes in the optical signal with an extreme spatial, spectral, and temporal sensitivity.
In more detail, we will develop an experimental setup that will combine the generation of ultrabroadband pulses in the MIR spectral region (from 2.5 to 15 μm wavelength) with their coherent superposition for 2D-MIR TDS. Our approach will allow the full detection of the sample response via direct detection in amplitude and phase of the light field by means of electro-optical sampling of the MIR pulses, whose duration is below 100 fs. We will apply our broadband MIR pulses to detect relevant biomolecules (e.g., proteins such as the transcription factor GCN4, or the neurodegenerative biomarkers α-synuclein) in the so called "molecular finger-print region". This project is part of the European project 'iSenseDNA' (grant agreement n. 101046920).
About the European project "Computation driven development of novel in vivo-like-DNA-nanotransducers for biomolecules structure identification"
iSenseDNA will provide a revolutionary technology for next-generation nano-biosensing, sensitive to target in real-time conformational changes and link molecular structure and biological function. By harnessing tailor-made circular supercoiled DNA as "transducers" and their dynamical interactions with proteins, we aim to develop an unprecedented and disruptive approach for real-time bio-molecular sensing that can transform medical diagnostics and treatment.