Biology subjects

Ghaemmaghami, A. M.

Publications and source records attributed to Ghaemmaghami, A. M..

4 recordsLinked to original sources

bioRxiv2020

MicroRNA-511-3p mediated modulation of the peroxisome proliferator-activated receptor gamma (PPARγ) controls LPS-induced inflammatory responses in human monocyte derived DCs

The peroxisome proliferator activated receptor gamma (PPAR{gamma}) is a ligand activated transcription factor expressed in dendritic cells (DCs), where it exerts anti-inflammatory responses against TLR4-induced inflammation. Recently, microRNA-511 (miR-511) has also emerged as a key player in controlling TLR4-mediated signalling, and in regulating the function of DCs. Interestingly, PPAR{gamma} has been previously highlighted as a putative target of miR-511 activity; however the link between miR-511 and PPAR{gamma} and its influence on human DC function within the context of LPS-induced inflammatory responses is unknown. Using a selection of miR-511-3p-specific inhibitors and mimics, we demonstrate for the first time that up or downregulation of miR-511-3p inversely correlates with PPAR{gamma} mRNA levels and transcriptional activity following treatment with PPAR{gamma} synthetic agonist rosiglitazone (RSG), in the presence or absence of LPS. Additionally, we show that PPAR{gamma} activation with RSG modulates LPS-induced DC activation and downregulates pro-inflammatory cytokine production following downregulation of miR-511-3p. Lastly, PPAR{gamma} activation was shown to suppress LPS-mediated induction of indoleamine 2,3-dioxygenase (IDO) activity in DCs, most likely due to changes in miR-511-3p expression. These data suggest that PPAR{gamma}-induced modulation of DC phenotype and function is influenced by miR-511-3p expression, which may serve as a potential therapeutic target against inflammatory diseases.

immunology↗

bioRxiv2020

Topographical biomaterials instruct bacterial surface attachment and the in vivo host-pathogen response

Bio-instructive materials that prevent bacterial biofilm formation and drive an appropriate host immune response have the potential to significantly reduce the burden of medical device-associated infections. Since bacterial surface attachment is known to be sensitive to surface topography, we experimentally survey 2,176 combinatorially generated shapes using an unbiased high-throughput micro topographical screen on polystyrene. This identifies topographies that reduce colonization in vitro by up to 15-fold compared with a flat surface for both motile and non-motile bacterial pathogens. Equivalent reductions are achieved on polyurethane, a polymer commonly used in medical devices. Using machine learning methods, a set of design rules based on generalisable descriptors is established for predicting bacteria-resistant micro topographies. In a murine foreign body infection model, anti-attachment topographies are shown to be refractory to P. aeruginosa and to recruit a productive host response, highlighting the potential of simple topographical patterning of non-eluting implants for preventing medical device associated infections.

microbiology↗

bioRxiv2020

Synergistic Material-Topography Combinations to Achieve Immunomodulatory Osteogenic Biomaterials

Human mesenchymal stem cells (hMSCs) are widely represented in ongoing regenerative medicine clinical trials due to their ease of autologous implantation. In bone regeneration, crosstalk between macrophages and hMSCs is critical with macrophages playing a key role in the recruitment and differentiation of hMSCs. However, engineered biomaterials able to both direct hMSC fate and modulate macrophage phenotype have not yet been identified. A novel combinatorial chemistry-microtopography screening platform, the ChemoTopoChip, is used to identify materials suitable for bone regeneration by screening with human immortalized mesenchymal stem cells (hiMSCs) and human macrophages. The osteoinduction achieved in hiMSCs cultured on the "hit" materials in basal media is comparable to that seen when cells are cultured in osteogenic media, illustrating that these materials offer a materials-induced alternative in bone-regenerative applications. These also exhibit immunomodulatory effects, concurrently polarizing macrophages towards a pro-healing phenotype. Control of cell response is achieved when both chemistry and topography are recruited to instruct the required cell phenotype, combining synergistically. The large library of materials reveals that the relative roles of microtopography and material chemistry are similar, and machine learning identifies key material and topographical features for cell-instruction.

bioengineering↗

bioRxiv2018

Holographic optical trapping Raman micro-spectroscopy for interacting live cells

We present a combined holographic optical tweezers and confocal Raman spectroscopy instrument which allows fast, flexible, and interactive manipulation with molecular measurement of interacting live cell systems. Multiple laser foci created using a spatial light modulator are simultaneously used for optical trapping and spontaneous Raman spectroscopy. To enable confocal Raman measurements with high spectral resolution, a digital micro-mirror device was used to generate reflective pinholes which are matched to each laser trap. We demonstrate this unique capability by initiating complex interactions between multiple live cells whilst non-invasively acquiring Raman spectra of the processes with high spatial, spectral, and temporal resolution.

biophysics↗