Ion Mobility Mass Spectrometry
Ion mobility mass spectrometry (IMMS) is a powerful analytical technique that is increasingly being used in the field of structural biology. Ion mobility separates ions according to shape and allows the study of conformational changes in biological systems that are not amenable to analysis by more established biophysical methods.
When coupled to mass spectrometry, ion mobility allows one to distinguish between co-existing forms of a protein, which cannot easily be achieved by other approaches.
Type IV Secretion Systems
The emergence of methicillin-resistant Staphylococcus aureus (MRSA), responsible
for difficult-to-treat infections in humans has led to the identification of broad-host-range
plasmids carrying antibiotic resistance, conjugated through Type IV Secretion Systems (T4SSs).
The T4SS is one of several types of secretion systems that mediates the transport of macromolecules
across cellular membranes. They are extremely versatile: found in both Gram-negative and Gram-positive
bacteria as well as some archaea, they are responsible for secreting a wide range of substrates,
including monomeric proteins, multisubunit protein toxins and nucleoprotein complexes.
The way proteins fold is of paramount importance. A number of
diseases are the result of protein misfolding and subsequent
aggregation. The list of these diseases include Alzheimer’s,
Prion diseases, etc. In our lab we are interested in alpha 1-antitrypsin (A1AT),
which is the archetype of the serpin (serine protease inhibitor) superfamily of proteins. It is predominantly synthesized in
hepatocytes and secreted into the circulation at the highest levels of any serum antiprotease. Under physiological conditions it protects the lungs from human
neurophil elastase but upon aggregation it is implicated in chirosis of the liver and
chronic obstructive pulmonary disease.