Variables, medidas y manipulaciones

The standard IVG model of TB showed the upregulation of MMPs in TB and then the 3D IVG demonstrated the functional activity of MMPs in degrading ECM and therefore leading to cell death. I believe we can develop this model further and examine the effect of different matrices in the 3D environment. The model can be developed in diverse ways, for example by incorporating different matrices or different cell types. For example, I could incorporate more cell types such as fibroblasts. Fibroblasts have been shown to be an important contributor to granuloma formation in human pulmonary TB (O'Kane C et al., 2007), and therefore incorporation may help more human-like granulomas to develop. Fibroblasts used in the model should be derived from same donor of PBMCs to avoid host immune cells reacting to MHC molecules expressed on fibroblasts.

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I took part in further developing the EVG model and the results obtained so far are promising. The bioelectrosprayer can be utilised in cell culture experiments with improved readouts such as cell survival, matrix breakdown and Mtb growth studies. Developing a model where all these different parameters are involved together will allow dissecting the TB pathogenesis in greater detail and maximise the number of readouts per well.

So in summary, although I have demonstrated that the ECM regulates cellular responses in TB, there is extensive further work that I would like to do to develop these findings, both from understanding the basic biology of how cell-matrix interactions control cellular behaviour to translational aspects whereby preventing excessive matrix breakdown may improve outcomes in TB.

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