Our lab has three main interests. (1) Time-resolved cryo-electron microscopy. How can we understand how proteins work as a function of time? To do this we are developing new techniques for time-resolved specimen preparation in cryo-electron microscopy and cryo-electron tomography. (2) Ionotropic glutamate receptors regulate the majority of excitatory neurotransmission. How do they function? How do they assemble into functional units? What is the mechanistic basis of their contribution to neurological disease? How can we leverage this information for therapeutic design? (3) The architecture of tight junctions and mechanisms of tight junction function. How do tight junctions form selective barriers for tissues? How are they dysregulated in diseases such as cancer and neurodegeneration, as well as aging?
We study these fundamental questions with a combination of cryo-electron microscopy, cryo-electron tomography, biochemistry, computation, and cell biology.
Please visit the lab website, http://twomeylab.com/, for more information.
Twomey, E.C.*, Ji, Z.*, Wales, T.E., Bodnar, N.O., Ficarro, S.B., Marto, J.A., Engen, J.R., Rapoport, T.A. “Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin unfolding.” Science, Aug 2;365(6452). pii: eaax1033. PMID: 31249135.
Twomey, E.C., Yelshanskaya, M.V., Vassilevski, A.A., Sobolevsky, A.I. “Mechanisms of channel block in calcium-permeable AMPA receptors.” Neuron, 99: 956-968 (2018). PMID: 30122377. Featured as issue cover.
Twomey, E.C., Yelshanskaya, M.V., Grassucci, R.A., Frank, J., Sobolevsky, A.I. “Channel opening and gating mechanism in AMPA-subtype glutamate receptors.” Nature, 549: 60-65 (2017). PMID: 28737760.
Twomey, E.C., Yelshanskaya, M.V., Grassucci, R.A., Frank, J., Sobolevsky, A.I. “Structural Bases of Desensitization in AMPA Receptor-Auxiliary Subunit Complexes.” Neuron, 94: 569-580 (2017). PMID: 28472657.
Twomey, E.C., Yelshanskaya, M.V., Grassucci, R.A., Frank, J., Sobolevsky, A.I. “Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy.” Science, 353: 83-86 (2016). PMID: 27365450.