Research projects within the Maj group
Ultrafast laser spectroscopy
The interaction between light and matter opens a vast window to acquire critical information about various systems, making spectroscopy an invaluable tool in the investigation of chemical and biological samples.
In our group, we are interested in answering fundamental question in physical chemistry and biophysics, focusing both on small molecules and proteins. To this end, we employ time-resolved infrared spectroscopy across time scales ranging from femtoseconds to milliseconds. Our principal methodologies include infrared transient absorption spectroscopy, two-dimensional infrared spectroscopy, and transient two-dimensional infrared spectroscopy. In addition to that, we are also interested in technique development, with particular focus on developing surface-enhanced two-dimensional spectroscopy and novel methods that integrate electrochemistry with spectroscopy.
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. Additionally, we employ cryo-electron microscopy (cryo-EM) to solve the structure of amyloid fibril polymorphs. Structural models of both the fibrils and 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.
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, we investigate the structure and photochemistry of phytochromes by employing ultrafast time-resolved infrared absorption spectroscopy and femtosecond serial X-ray crystallography.
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.
Photophysics and photochemistry of prebiotic Earth
How the nucleotides that make up DNA may have formed on prebiotic Earth is a central question in contemporary chemistry. DNA is the building block for all living things on our planet, but the chemical and physical processes that led to the emergence of life are a matter of long dispute. The constituents of DNA and RNA are photostable under UV irradiation, which indicates that they may be final products of photochemical reactions that had been triggered by a continuous exposure to UV light on early Earth.
In collaboration with Dr Rafal Szabla from the Univ. of Edinburgh, we use femtosecond transient IR spectroscopy and high-level QM calculations to elucidate the structural origins of such exceptional photostability of nucleotides and to discover possible pathways that lead to their prebiotic synthesis.
Contact
- If you have any questions regarding our research, you are welcome to contact Michal Maj.
- Michal Maj