Transgutaminase-2-mediated protein cross-linking involves an isopeptide bond formation between two cellular substrates: a gamma carboxamide group of a peptide-bound Gln residue and the epsilon-amino group of a peptide-bound Lys residue or a primary amino group of a polyamine. Protein deamidation of Gln residues by TG2 contributes to the development of disorders caused by gluten sensitivity. The expression and activation of TG2 is believed to occur as a response to tissue "injury" and the enzyme is tightly controlled by the redox state affecting the Cys active site. TG2 is ubiquitous and externalised via extracellular vesicles in many cell types. Our laboratory has a long history of specialistic research on this enzyme family: many of the methods now commercially available were developed at NTU. We are leaders in the field.
From conventional cell monolayers, our research is moving towards three-dimensional cell models, organoids and organoids on chips, which re-create a physiological mocroenvironment including tissue-specific endothelial cells. Organ-Chips combine cell culture with microfluidics and are provided to us by Emulate in collaboration with Dr Hatziapostolou (NTU).
Human iPSCs (induced pluripotent stem cells) are cells obtained from human adult cells (for example, skin cells) after a process called "reprogramming" that brings them back to an embryonal state. From this state, they can be turned, or "differentiated", into any cell you want. We can use this methodology to generate brain cells, such as neurons and astrocytes, starting from the skin cells of people living with dementia or other diseases, obtaining highly translatable results in the study of human physiology and pathology.
We do study the extracellular environment, the extracellular matrix (ECM), biofluids, extracellular vesicles (EV) and outside-in biosignalling. We perform isolation of EVs from a wide range of biofluids (urine, plasma, serum, exhaled breath condensate), cell conditioned medium and even milk. We characterise EVs according to MISEV and rely on Nanoparticle tracking analysis, single EV quantification of cargo molecules, EVs QPCR, proteomics, transcriptomics, EV enzymatic activities, and microscopy (TEM, AFM, Nanolive).