Phill Stansfeld publications
The energetics of protein-lipid interactions as viewed by molecular simulations
Corey RA, Stansfeld PJ, Sansom
Membranes are formed from a bilayer containing diverse lipid species with which membrane proteins interact. Integral, membrane proteins are embedded in this bilayer, where they interact with lipids from their surroundings, whilst peripheral membrane proteins bind to lipids at the surface of membranes. Lipid interactions can influence the function of membrane proteins, either directly or allosterically. Both experimental (structural) and computational approaches can reveal lipid binding sites on membrane proteins. It is, therefore, important to understand the free energies of these interactions. We summarise the current state of the field and provide an outlook on likely future directions of investigation.
Multiple Lipid Binding Sites Determine the Affinity of PH Domains for Phosphoinositide-Containing Membranes
Eiji Yamamoto, Jan Domański, Fiona B Naughton, Robert B Best, Antreas C Kalli, Phillip J Stansfeld and Mark SP Sansom
NAssociation of peripheral proteins with lipid bilayers regulates membrane signaling and dynamics. Pleckstrin homology (PH) domains bind to phosphatidylinositol phosphate (PIP) molecules in membranes. The effects of local PIP enrichment on the interaction of PH domains with membranes is unclear. We describe a mechanism of PH binding proceeding via an encounter state to two bound states which differ in the orientation of the protein relative to the membrane, these orientations depending on the local PIP concentration. These results suggest that nanoscale clustering of PIP molecules can control the strength and orientation of PH domain interaction in a concentration-dependent manner.
Data Mining a Medieval Medical Text Reveals Patterns in Ingredient Choice That Reflect Biological Activity against Infectious Agents
Erin Connelly, Charo I. del Genio, Freya Harrison
The pharmacopeia used by physicians and laypeople in medieval Europe has largely been dismissed as placebo or superstition. While we now recognize that some of the materia medica used by medieval physicians could have had useful biological properties, research in this area is limited by the labor-intensive process of searching and interpreting historical medical texts. In providing a worked example of data-driven textual analysis, we demonstrate the potential of this approach to encourage interdisciplinary collaboration and to shine a new light on the ethnopharmacology of historical medical texts.
Johannes Boltze publications
The emergence of dyslexia in the developing brain
Kuhl U., Neef N.E., Kraft I., Schaadt G., Dörr L., Brauer J., Czepezauer I., Müller B., Wilcke A., Kirsten H., Emmrich F., Boltze J., Friederici A.D., Skeide M.A.
Developmental dyslexia, a severe deficit in literacy learning, is a neurodevelopmental learning disorder. Yet, it is not clear whether existing neurobiological accounts of dyslexia capture potential predispositions of the deficit or consequences of reduced reading experience. Here, we longitudinally followed 32 children from preliterate to school age using functional and structural magnetic resonance imaging techniques. Our results provide evidence for the notion that dyslexia may originate from an atypical maturation of the speech network that precedes literacy instruction.
Bone marrow mononuclear cells activate angiogenesis via gap junction mediated cell-cell interaction
Kikuchi-Taura A. Okinaka Y., Takeuchi Y., Ogawa Y., Maeda M., Kataoka Y., Yasui T., Kimura T., Gul S., Claussen C., Boltze J., Taguchi A
Bone marrow mononuclear cells (BM-MNCs) are a rich source of hematopoietic stem cells and have been widely used in experimental therapies for patients with ischemic diseases. The objective of this study is to reveal the mechanism how BM-MNCs activate angiogenesis. Our findings demonstrated cell-cell interaction via gap junction is the prominent pathway for activation of angiogenesis at endothelial cells after ischemia and provided novel paradigm that energy source supply by stem cell to injured cell is one of the therapeutic mechanisms of cell-based therapy.
Model evaluation of target product profiles of an infant vaccine against respiratory syncytial virus (RSV) in a developed country setting
Timothy Kinyanjui, Wirichada Pan-Ngum, Sompob Saralamba, Sylivia Taylor, Lisa White, D James Nokes
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract disease in children worldwide and is a significant cause of hospital admissions in young children in England. No RSV vaccine has been licensed but a number are under development. In this work, we present two structurally distinct mathematical models, parameterized using RSV data from the UK, which have been used to explore the effect of introducing an RSV paediatric vaccine to the National programme.
Assessment of the Potential of Vaccination to Combat Antibiotic Resistance in Gonorrhea: A Modeling Analysis to Determine Preferred Product Characteristics
Lilith K Whittles, Peter J White, Xavier Didelot
Gonorrhea incidence is increasing rapidly in many countries, whilst antibiotic resistance is making treatment more difficult. Combined with evidence that MeNZB and Bexsero meningococcal vaccines are likely partially-protective against gonorrhea, this has renewed interest in a gonococcal vaccine, and several candidates are in development. Key questions are how protective a vaccine needs to be, how long protection needs to last, and how should it be targeted. We assessed vaccination’s potential impact, and the feasibility of achieving WHO’s target 90% reduction in gonorrhea incidence 2016-2030, by comparing realistic vaccination strategies under a range of scenarios of vaccine efficacy and duration of protection, and emergence of extensively-resistant gonorrhea.
Role of A1 receptor-activated GIRK channels in the suppression of hippocampal seizure activity
Hill E, Hickman C, Diez R, Wall M.
The neuromodulator adenosine is released during seizure activity to provide negative feedback suppression of ongoing activity and to delay the occurrence of the next burst of activity. Adenosine acts via multiple G-protein-coupled receptors including the A1 receptor (A1R) which inhibits neurotransmitter release and hyperpolarises neuronal membrane potential. The hyperpolarisation is produced, at least in part, by the activation of G-protein-activated inwardly rectifying K+ (GIRK) channels. We have used tertiapin-Q (TQ), a potent and selective inhibitor of GIRK channels, to assess the role of GIRK channels in controlling seizure activity. Our results show that GIRK channels play a role in the supressing effects of adenosine on seizure activity.