hollow-fiber-bioreactors-for-in-vivo-like-mammalian-tissue-culture

Hollow Fiber Bioreactors for <em>In Vivo</em>-like Mammalian Tissue Culture

Tissue culture has been used for over 100 years to study cells and responses ex vivo. The convention of this technique is the growth of anchorage ...

University of Liverpool

Many parasites and pathogens cause silent/covert infections in addition to the more obvious infectious disease-causing pathology. Here, we consider how assumptions concerning superinfection, protection and seasonal host birth and transmission rates affect the evolution of such covert infections as a parasite strategy. Regardless of whether there is vertical infection or effects on sterility, overt infection is always disadvantageous in relatively constant host populations unless it provides protection from superinfection. If covert infections are protective, all individuals will enter the covert stage if there is enough vertical transmission, and revert to overt infections after a 'latent' period (susceptible, exposed, infected epidemiology). Seasonal variation in transmission rates selects for non-protective covert infections in relatively long-lived hosts with low birth rates typical of many mammals. Variable host population density caused by seasonal birth rates may also select for covert transmission, but in this case it is most likely in short-lived fecund hosts. The covert infections of some insects may therefore be explained by their outbreak population dynamics. However, our models consistently predict proportions of covert infection, which are lower than some of those observed in nature. Higher proportions of covert infection may occur if there is a direct link between covert infection and overt transmission success, the covert infection is protective or the covert state is the result of suppression by the host. Relatively low proportions of covert transmission may, however, be explained as a parasite strategy when transmission opportunities vary.

The evolution of covert, silent infection as a parasite strategy.

This study is motivated by understanding and controlling the key physical properties underlying internalisation of nano drug delivery. We consider the internalisation of specific nanometre size delivery vehicles, comprised of self-assembling amphiphilic block copolymers, called polymersomes that have the potential to specifically deliver anticancer therapeutics to tumour cells. The possible benefits of targeted polymersome drug delivery include reduced off-target toxic effects in healthy tissue and increased drug uptake by diseased tissue. Through a combination of in vitro experimentation and mathematical modelling, we develop a validated model of nanoparticle uptake by cells via the clathrin-mediated endocytotic pathway, incorporating receptor binding, clustering and recycling. The model predicts how the characteristics of receptor targeting, and the size and concentration of polymersomes alter uptake by tumour cells. The number of receptors per cell was identified as being the dominant mechanism accounting for the difference between cell types in polymersome uptake rate.

Article	Year
The evolution of covert, silent infection as a parasite strategy. Proceedings. Biological sciences / The Royal Society\| PubMed ID: 19324776	2009
Combined mathematical modelling and experimentation to predict polymersome uptake by oral cancer cells. Nanomedicine : nanotechnology, biology, and medicine\| PubMed ID: 24036098	2014

Ian Sorrell

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