Circulatory zinc transport occurs at distinct interdomain sites on mammalian albumins

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Locations of zinc-binding sites on equine serum albumin.

Zinc is an essential nutrient in the body that is required for virtually all biological processes, therefore its homeostasis and trafficking is of fundamental interest. Serum albumin is the major carrier of Zn2+ in the blood and is required for its systemic distribution. In collaboration with Prof. Wladek Minor (University of Virginia), Dr Maksymilian Chruszcz (University of South Carolina) and Dr Claudia Blindauer (University of Warwick), the Stewart lab present the first crystal structures of human serum albumin (HSA) and equine serum albumin (ESA) in complex with Zn2+. The structures allow unambiguous identification of the major zinc binding site on these two albumins, as well as several further, weaker zinc binding sites. Furthermore, analysis of Zn2+ binding to HSA and ESA proved the presence of secondary sites with 20-50-fold weaker affinities, which may be important under certain physiological conditions. Collectively, these findings are critical to our understanding of the role serum albumin plays in circulatory Zn2+ handling and cellular delivery. The new findings are published in the open-access journal, Chemical Science. Full text of the article is available here.

Visit to Fight for Sight HQ

Dr Alan Stewart visited Fight for Sight yesterday, together with Dr Imre Lengyel (UCL Institute of Ophthalmology) to update the charity on the recent progress made on their Fight for Sight project grant.

They were excited to meet the FFS team who extended a warm welcome and gave insight into the great work that the charity does. In addition to fundraising and funding new research, the charity is committed to raising awareness of issues surrounding visual impairment and informing on new developments in the field. Drs Stewart and Lengyel are especially grateful to Dolores Conroy, Fight for Sight’s Director of Research, for the invitation to attend.

EU COST Action Meeting (Zinc-Net): Dietary supplements vs food biofortification and the gut microbiome, Sofia, Bulgaria.

zinc-netDr Alan Stewart would like to thank the organisers (Profs. Nicky Lowe, Fernando Lidon and Radostina Alexandrova) of the EU COST Action Meeting (Zinc-Net TD1304) on dietary supplements vs food biofortification and the gut microbiome, which took place on the 22nd/23rd March 2016 in Sofia, Bulgaria. Dr Stewart presented his work relating to the interplay between fatty acids and plasma zinc status and the implications of this dynamic for zinc bioavailability. In addition, he acted as rapporteur (together with Dr José C. Ramalho, Universidade de Lisboa) for the third scientific session on “Zinc Biofortification”.

Is eye research the best kept secret?

In a recent article published in the RNIB (Royal National Institute of Blind People) magazine Julian Jackson, a Senior Adviser at Fight for Sight, argues that scientists working in the field of vision research need to better communicate the work they do to eye health professionals, patients and the public. A link to the article can be found here.

To help to address this Fight for Sight have established a Speaker Network, made up of over 100 academic researchers, clinician scientists and clinicians offering a wide range of expertise and experience. The aim of the network is to target large annual conferences, AGM’s and key optical events as well as regional and local meetings to ensure maximum reach and penetration of the charity’s message about the critical importance of eye research.

Phospholipase C-η2 activity is required for neurite growth

 

Visualisation of PLCη2-LIMK1 interactions in Neuro2A cells within growting neurites using a proximity ligand assay.
Direct visualisation of PLCη2-LIMK1 interactions (red dots) in Neuro2A cells within growing neurites using a proximity ligand assay. Interactions can also be seen in the cell body and nucleus (stained blue).

Phosphatidylinositol (PhoIns)-specific phospholipase C enzymes (PLCs) are central to the inositol lipid signalling pathways and contribute to intracellular Ca2+ release and protein kinase C activation in mammalian neurons. Six distinct classes of PhoIns-specific PLCs are known to exist in mammals (β, γ, δ, ε, ζ, and η), all of which are activated by distinct membrane receptor-mediated events. The Stewart lab previously revealed that expression of the PLC isozyme, PLC-η2 is essential for neurite growth, a process central to normal neuronal differentiation. A new study from the lab has gone a step further and shown that active PLC-η2 is needed for neurite growth to occur. Furthermore, the study also revealed that PLC-η2 interacts directly with LIM Domain Kinase 1, a key cytoskeletal regulatory protein previously implicated in this process. The new findings are published in the journal, Histochemistry and Cell Biology. Full text is available here: DOI 10.1007/s00418-015-1390-7.

Alan Stewart Appointed to BBSRC Pool of Experts

Dr Alan Stewart has been appointed to the BBSRC Pool of Experts. The BBSRC is one of the 7 Research Councils that work together as Research Councils UK (RCUK). The BBSRC which funds world leading UK bioscience has an annual budget in excess of £500M. Pool members are appointed based upon an active involvement in high quality UK biological research, and are recruited from a range of scientific backgrounds to assist in the assessment of funding applications.

29th Annual Conference of the EMDS 2015

IMG_20150923_112803Dagmara Wiatrek was in attendance at the 29th European Macrophage and Dendritic Cell Society (EMDS) Meeting in Krakow, Poland. Dagmara presented a poster entitled “Alterations in zinc transporter expression during dendritic cell maturation”. Her trip was supported by a travel award from EMDS.dagmara