Dr Rene Frank
Independent Investigator Scientist
I am 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 various forms of synaptic plasticity and synaptogenesis. I am 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 Aβ and tau pathologies? To address these questions I am using genetically engineered mice and in vivo protein labelling methods.
Associated News Items
Frank RA, Komiyama NH, Ryan TJ, Zhu F, O'Dell TJ, Grant SG (2016), “NMDA receptors are selectively partitioned into complexes and supercomplexes during synapse maturation.” Nat Commun 7:11264
Frank RA, Grant SG (2017), “Supramolecular organization of NMDA receptors and the postsynaptic density.” Curr Opin Neurobiol 45:139-147
Frank RA, Zhu F, Komiyama NH, Grant SG (2017), “Hierarchical organisation and genetically separable subfamilies of PSD95 postsynaptic supercomplexes” J Neurochem
Frank RA (2011), “Endogenous ion channel complexes: the NMDA receptor.” Biochem Soc Trans 39(3):707-18 Details
Frank RA, 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 (2011), “Clustered coding variants in the glutamate receptor complexes of individuals with schizophrenia and bipolar disorder.” PLoS One 6(4):e19011 Details
Frank RA, Kay CW, Hirst J, Luisi BF (2008), “Off-pathway, oxygen-dependent thiamine radical in the Krebs cycle.” J Am Chem Soc 130(5):1662-8 Details
Frank RA, Leeper FJ, Luisi BF (2007), “Structure, mechanism and catalytic duality of thiamine-dependent enzymes.” Cell Mol Life Sci 64(7-8):892-905 Details
Frank RA, Price AJ, Northrop FD, Perham RN, Luisi BF (2007), “Crystal structure of the E1 component of the Escherichia coli 2-oxoglutarate dehydrogenase multienzyme complex.” J Mol Biol 368(3):639-51 Details
Frank RA, Pratap JV, Pei XY, Perham RN, Luisi BF (2005), “The molecular origins of specificity in the assembly of a multienzyme complex.” Structure 13(8):1119-30 Details
Frank RA, Titman CM, Pratap JV, Luisi BF, Perham RN (2004), “A molecular switch and proton wire synchronize the active sites in thiamine enzymes.” Science 306(5697):872-6 Details