Group moving from Cambridge to Leeds 3 September 2018.
The ‘wiring’ of neuronal circuits in the brain is mediated by synapses, which are responsible for processing and storing information. We are interested in understanding the native molecular architecture of synapses with a particular focus on postsynaptic membranes that contain N-methyl D-aspartic acid receptors (NMDARs).
NMDARs mediate Ca2+-dependent signalling, acting in concert with a complex repertoire of synaptic proteins to initiate synaptogenesis and various forms of synaptic plasticity. We are using mouse genetics in combination with novel biochemical methods, fluorescence imaging, and cryo-electron tomography. This integrated approach allows us to investigate the postsynaptic membrane directly and test its molecular mechanisms in vivo.
Allied to the basic biology are key questions regarding synapses in Alzheimer’s disease (AD). Particularly, what signalling mechanisms are involved in the loss of glutamatergic synapses in AD, and how these are linked to A? and tau pathologies? To address these questions we are using genetically engineered mice and in vivo protein labelling methods.
Almeida-Souza L, Frank RAW, Garcia-Nafria J, Colussi A, Gunawardana N, Johnson CM, Yu M, Howard G, Vallis Y, McMahon HT.
A flat BAR domain protein promotes actin polymerization at the base of clathrin-coated pits.
Cell 174, 1-13. (2018).
Fernandez E, Collins, MO, Frank RA., Zhu F, Kopanitsa MV, Nithianantharajah J, Lemprière SA, Fricker D, Elsegood KA, McLaughlin CL, Croning MDR, Mclean C, Armstrong JD, Hill WD, Deary IJ, Cencelli G, Bagni C, Fromer M, Purcell SM, Pocklington AJ, Choudhary JS, Komiyama NH, Grant SGN.
Arc Requires PSD95 for Assembly into Postsynaptic Complexes Involved with Neural Dysfunction and Intelligence.
Cell Reports 45, 139-147. (2017).
Frank RAW, Grant SGN.
Supramolecular organisation of NMDA receptors and the postsynaptic density.
Current Opinions in Neurobiology 142, 139-147. (2017).
Frank RAW, Komiyama NH, Grant SGN. Hierarchical organisation and genetically separable subfamilies of PSD95 postsynaptic supercomplexes.
Journal of Neurochemistry 142, 504-511. (2017).
Frank RAW, Komiyama NH, Ryan TJ, Zhu F, O’Dell T, Grant SGN.
NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation.
Nature Communications 7, 11624. (2016).
Endogenous ion channel complexes: the NMDA receptor
Biochemical Society Transactions 39, 707. (2011).
Frank RAW, McRae AF, Pocklington AJ, van de Lagemaat LN, Navarro P, Croning MD, Komiyama NH., Bradley SJ, Challiss RA, Armstrong JD, Finn RD, Malloy MP, MacLean AW, Harris SE, Starr JM, Bhaskar SS, Howard EK, Hunt SE, Coffey AJ, Ranganath V, Deloukas P, Rogers J, Muir WJ, Deary IJ, Blackwood DH, Visscher PM, Grant SG.
Clustered coding variants in the glutamate receptor complexes of individuals with schizophrenia and bipolar disorder.
PLoS One 6, e19011. (2011).
Pei XY, Titman CM, Frank RAW, Leeper FJ, Luisi BF.
Snapshots of catalysis in the E1 subunit of the pyruvate dehydrogenase multienzyme complex.
Structure 16, 1860. (2008).
Frank RAW, Kay C, Hirst J, Luisi BF.
An off-pathway, thiamine-dependent radical in the Krebs cycle.
Journal of the American Chemical Society 30, 1662. (2008).
Frank RAW, Leeper F, Luisi BF.
Structure, mechanism and catalytic duality of thiamine-dependent enzymes.
Cellular and Molecular Life Sciences 64, 892. (2008).
Frank RAW, Price A, Northrop F, Perham RN, Luisi BF.
Crystal structure of the E1 component of the Escherichia coli 2-oxoglutarate
dehydrogenase multienzyme complex.
Journal of Molecular Biology 368, 63. (2007).
Frank, RAW, Pratap V, Yuan Pei X, Luisi BF, Perham RN.
The molecular origin of specificity in the assembly of a multienzyme complex.
Structure 13, 1119 (2005).
Frank RAW, Pratap V, Titman C, Luisi BF, Perham RN.
A molecular switch and proton-wire synchronize the active sites in thiamine enzymes.
Science 306, 872-876. (2004).