Ultrafast Laser Spectroscopy
Our group applies ultrafast laser spectroscopic techniques and structural biology methods in a search for answers to fundamental questions in chemistry and biophysics.
The structure and function of molecules are largely determined by the way their chemical bonds move and interact with each other. Chemical bonds are dynamic entities, exhibiting collective structural changes on timescales as short as a trillionth of a second.
The ultrashort pulsed lasers used in our laboratory are designed to observe such fast events, both under equilibrium conditions and following an instantaneous external perturbation. Our scientific interests span a broad range of subjects, studied on both the molecular and cellular levels.
Protein-Misfolding in Human Diseases
Many human diseases are caused by aggregation of misfolded proteins into amyloid fibrils. The proteins are often essential hormones, which play a vital role in regulating various metabolic processes in the body.
It is not fully understood what causes their spontaneous self-assembly and how the aggregation contributes to the development of the disease. In many diseases, the aggregation process occurs through the formation of small, toxic intermediates.
In our group, we take advantage of the rapid acquisition of femtosecond two-dimensional infrared (2D IR) spectroscopy to study the structure and aggregation kinetics of the toxic intermediate formed by the human islet amyloid polypeptide (hIAPP) – the pancreatic hormone linked to the beta-cell loss in type II diabetes. Structural models of the intermediate species will advance our understanding of amyloid diseases and open up for development of new ways of preventing and treatment of type 2 diabetes as well as other diseases that occur due to misfolding, aggregation, and accumulation of proteins.
Developing Vibrational Sensors of Protein Structure
Infrared (IR) spectroscopy can provide a great level of detail about protein structure and dynamics. It is due to the fact that vibrational motions of the protein backbone are highly sensitive to the nature and strength of hydrogen bonding interactions.
It is not difficult to determine the secondary structure composition of a protein from its IR spectra, but the lack of residue-level resolution prevents the technique from reaching its full potential.
Our group aims at overcoming these limitations by developing new molecular probes that can be introduced site-specifically into a protein side-chain.
The molecular probes designed in our group act as highly sensitive sensors of the local environment and may help us understand the structural origins of enzyme activity and unravel how the solvation structure and ultrafast conformational fluctuations at a local site influence the protein function.
Signaling Mechanisms in Plant Photoreceptors
The ability to sense and respond to the surrounding environmental changes is crucial for the sustainability of living organisms. Both plants and animals use a variety of light-responsive proteins to sense light, one of the most important environmental stimuli on Earth.
These proteins are generally known as photoreceptors. Sensitivity to light is caused by a covalently attached chromophore that alters its shape in response to light and subsequently induces a change in the protein conformation.
Some of the most extensively characterized plant photoreceptors are phytochromes, but the conformational changes that take place during the photosensing process in phytochromes are not fully understood. As part of a collaborative project with Prof. Sebastian Westenhoff (westenhofflab.net), we investigate the structure and photochemistry of phytochromes by employing ultrafast time-resolved infrared absorption spectroscopy and femtosecond serial X-ray crystallography.