Matt Sykes - Academia.edu (original) (raw)

Papers by Matt Sykes

Charlie Cook, CERN At CERN, physicists and engineers are probing the fundamental structure of the... more Charlie Cook, CERN At CERN, physicists and engineers are probing the fundamental structure of the universe. They use the world’s largest and most complex scientifi c instruments to study the basic constituents of matter – the fundamental particles. The particles are made to collide together at high energy, close to the speed of light. The process gives the physicists clues about how the particles interact, and provides insights into the fundamental laws of nature. The Large Hadron Collider (LHC) is the world’s largest and most powerful particle accelerator. It fi rst started up in 2008, and remains the latest addition to CERN’s accelerator complex. The LHC consists of a 27km ring of superconducting magnets to guide the stiff proton beams around the quasi-circular path of the machine, and through accelerating structures which boost the energy of the particles at each turn. Particle physics takes the long-term view. Originally conceived in the 1980s, the LHC took another 25 years to c...

This paper describes the role of civil engineering in the optimisation of the design of CERN’s Fu... more This paper describes the role of civil engineering in the optimisation of the design of CERN’s Future Circular Collider (FCC). The civil engineering team at CERN have employed a bespoke, interactive, geological tool to consider the suitability of multiple layout options for the FCC, situated in the Geneva Basin, in particular quasi-circular options with circumferences in the order of 100 km. The tool has been used to provide feedback on potential lattice designs that are assessed based on criteria such as geological risk, shaft depth and the environmental sensitivities of access and experimental sites. This paper presents the process and some results of the impact of civil engineering on the design of the FCC, in particular on the layout, location, and structural requirements, and also how the optimised design has been used as the basis for a cost and schedule study. INTRODUCTION The feasibility of a Future Circular Collider (FCC) at CERN as a successor to the Large Hadron Collider ...

Soft Matter, 2010

Some basic insights into force measurements with AFM are provided here to help the reader underst... more Some basic insights into force measurements with AFM are provided here to help the reader understand the measurements discussed in the manuscript.

Chemistry and Physics of Lipids, 2010

Cytochromes P450 (CYP) are key enzymes involved in the metabolism of drugs and other lipophilic x... more Cytochromes P450 (CYP) are key enzymes involved in the metabolism of drugs and other lipophilic xenobiotics and endogenous compounds. In this study, atomic force microscopy was applied to characterise the association of CYP2C9 to dimyristoylphosphatidylcholine (DMPC) supported phospholipid bilayers. CYP2C9 was found to exclusively localise in the gel domains of partially melted DMPC bilayers. Despite lacking the N-terminus transmembrane spanning domain, the CYP2C9 protein appeared to partially embed into the membrane bilayer, as evidenced by an increase in melting temperature of surrounding phospholipids. Reversible binding of CYP2C9 via an engineered His tag to a phospholipid bilayer was facilitated using nickel-chelating lipids, presenting potential applications for biosensor technologies.

ACS Medicinal Chemistry Letters, 2013

Human mitogen-activated protein kinases (MAPK)-interacting kinases 1 and 2 (Mnk1/2) are promising... more Human mitogen-activated protein kinases (MAPK)-interacting kinases 1 and 2 (Mnk1/2) are promising anticancer targets. Mnks possess special insertions and a DFDmotif that are distinct from other kinases. Crystallographic studies of Mnk1/2 have revealed that the DFD-motif adopts the DFG/D-out conformation in which residue F227 flips into the ATP binding pocket. This is rarely observed in other kinases. Although the DFG-out conformation has attracted great interest for designing selective inhibitors, structural requirements for binding and the mechanism governing the DFG-out conformation remain unclear. This work presents for the first time the applicability of 3D models of Mnk2 protein in studying conformational changes by utilizing homology modeling and molecular dynamics simulations. The study reveals that the interactions between residue K234 of insertion I1 and D226 of the DFD motif play a key role in inducing and stabilizing the DFD-out conformation. The structural features will aid in the rational design of Mnk2 inhibitors.

The Structural Engineer: journal of the Institution of Structural Engineer, 2015

Charlie Cook, CERN At CERN, physicists and engineers are probing the fundamental structure of the... more Charlie Cook, CERN At CERN, physicists and engineers are probing the fundamental structure of the universe. They use the world’s largest and most complex scientifi c instruments to study the basic constituents of matter – the fundamental particles. The particles are made to collide together at high energy, close to the speed of light. The process gives the physicists clues about how the particles interact, and provides insights into the fundamental laws of nature. The Large Hadron Collider (LHC) is the world’s largest and most powerful particle accelerator. It fi rst started up in 2008, and remains the latest addition to CERN’s accelerator complex. The LHC consists of a 27km ring of superconducting magnets to guide the stiff proton beams around the quasi-circular path of the machine, and through accelerating structures which boost the energy of the particles at each turn. Particle physics takes the long-term view. Originally conceived in the 1980s, the LHC took another 25 years to c...

This paper describes the role of civil engineering in the optimisation of the design of CERN’s Fu... more This paper describes the role of civil engineering in the optimisation of the design of CERN’s Future Circular Collider (FCC). The civil engineering team at CERN have employed a bespoke, interactive, geological tool to consider the suitability of multiple layout options for the FCC, situated in the Geneva Basin, in particular quasi-circular options with circumferences in the order of 100 km. The tool has been used to provide feedback on potential lattice designs that are assessed based on criteria such as geological risk, shaft depth and the environmental sensitivities of access and experimental sites. This paper presents the process and some results of the impact of civil engineering on the design of the FCC, in particular on the layout, location, and structural requirements, and also how the optimised design has been used as the basis for a cost and schedule study. INTRODUCTION The feasibility of a Future Circular Collider (FCC) at CERN as a successor to the Large Hadron Collider ...

Soft Matter, 2010

Some basic insights into force measurements with AFM are provided here to help the reader underst... more Some basic insights into force measurements with AFM are provided here to help the reader understand the measurements discussed in the manuscript.

Chemistry and Physics of Lipids, 2010

Cytochromes P450 (CYP) are key enzymes involved in the metabolism of drugs and other lipophilic x... more Cytochromes P450 (CYP) are key enzymes involved in the metabolism of drugs and other lipophilic xenobiotics and endogenous compounds. In this study, atomic force microscopy was applied to characterise the association of CYP2C9 to dimyristoylphosphatidylcholine (DMPC) supported phospholipid bilayers. CYP2C9 was found to exclusively localise in the gel domains of partially melted DMPC bilayers. Despite lacking the N-terminus transmembrane spanning domain, the CYP2C9 protein appeared to partially embed into the membrane bilayer, as evidenced by an increase in melting temperature of surrounding phospholipids. Reversible binding of CYP2C9 via an engineered His tag to a phospholipid bilayer was facilitated using nickel-chelating lipids, presenting potential applications for biosensor technologies.

ACS Medicinal Chemistry Letters, 2013

Human mitogen-activated protein kinases (MAPK)-interacting kinases 1 and 2 (Mnk1/2) are promising... more Human mitogen-activated protein kinases (MAPK)-interacting kinases 1 and 2 (Mnk1/2) are promising anticancer targets. Mnks possess special insertions and a DFDmotif that are distinct from other kinases. Crystallographic studies of Mnk1/2 have revealed that the DFD-motif adopts the DFG/D-out conformation in which residue F227 flips into the ATP binding pocket. This is rarely observed in other kinases. Although the DFG-out conformation has attracted great interest for designing selective inhibitors, structural requirements for binding and the mechanism governing the DFG-out conformation remain unclear. This work presents for the first time the applicability of 3D models of Mnk2 protein in studying conformational changes by utilizing homology modeling and molecular dynamics simulations. The study reveals that the interactions between residue K234 of insertion I1 and D226 of the DFD motif play a key role in inducing and stabilizing the DFD-out conformation. The structural features will aid in the rational design of Mnk2 inhibitors.

The Structural Engineer: journal of the Institution of Structural Engineer, 2015