ERC Research Group @ MPI Stuttgart
We are all made of molecules.
Our goal is to understand how they function.
A bedazzling medley of molecules interact to perform countless tasks essential to our life.
We are curious to know how complex molecules, such as proteins, carbohydrates, drugs, and vaccines, do their jobs.
We seek these answers by looking at their structures one-at-a-time.
ERC Project GlycoX
Aims to reveal the structures of molecules decorated with carbohydrates, using the combination of electrospray ion beam deposition and scanning probe microscopy (a.k.a ESIBD+SPM).
All cells are coated with carbohydrates (a.k.a glycans).
Glycans are essential to all life forms by carrying out important cell-cell communication in immune system or microbial infection (among many other functions).
Glycans broadcast the identity and the state of a cell to its surrounding. Due to these unique roles, glycans earn the nickname: the 'sugar code' i.e. the language used by cells to communicate - and by pathogens to infect.
Reading and understanding these mysterious sugar codes are the goals of many research projects today that seek to radically change our diagnostic and therapeutic approaches to many important health challenges facing our society today e.g. cancers and vaccines.
Reading the sugar code requires us to figure out the molecular structure of every glycan molecule present on a cell.
However, glycans are found multiply attached to another biomolecules, such as lipids or proteins, which cause their structural analysis to be very challenging. Analysis of these glycan-decorated molecules (a.k.a glycoconjugates) by today's analytical methods are difficult due to ensemble-averaging in these methods i.e. molecules are analyzed collectively, causing information loss at individual level.
Project GlycoX aims to address this analytical challenge by imaging glycoconjugate molecules one-at-a-time using the ESIBD+SPM approach.
To learn more, see an excellent introduction to the analytical challenge of glycans by Prof. Sabine Flitsch (link).
How does ESIBD+SPM work?
We transport molecules from a solution onto a surface in vacuum so that we can image them on surface one-at-a-time by single molecule microscopy.
Single Molecule Imaging
We are experiment + theory research group working at the junction between nanoscience, physical analytical chemistry, and glycoscience.
We unveil structures and interactions of complex biomolecules using ESIBD + SPM + DFT.
Experiment: We electrospray our target molecules as ions and soft land these ions on a single-crystal surface held at low temperatures (~120 K) in ultrahigh vacuum (UHV). We transfer our surface to our low temperature STM (ScientaOmicron Fermi SPM) to image the deposited molecules one-at-a-time at 11 K.
Theory: We perform our Density Functional Theory (DFT) calculations to model the observed molecules on surface. We use ORCA to model gas-phase ions, VASP to model molecules on surfaces, and OpenMX to model macromolecules.
We are interested in probing the electronic states of biomolecules using single molecule spectroscopy.
By examining the correlation between electronic and nuclear structures, we aim to develop a new method for single molecule analytical chemistry.
Using single molecule imaging, we are interested to determine the sequence of biomolecules that are very challenging for existing analytical methods.
Many of these biomolecules are complex polysaccharides and glycoproteins central in the diagnostics and therapeutics of many diseases.
We are interested to determine the folded structures of biomolecules that remain beyond the reach of today's ensemble-averaged structural determination techniques.
We image biomolecules and their ligand adducts, such as biomolecule-drug adduct, to determine how these biomolecules interact with their partners.