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SUMMARY:Protein Design: in biro\, in silico\, in vitro and in vivo
DTSTART:20171002T121500
DTSTAMP:20261001T160916Z
UID:d9bb08a20d5426c83f815267c2c3ee7f88d2b1bb7ac7d395b26dec15
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Dek Woolfson\, University of Bristol\, Bristol (UK)\nDIS
 TINGUISHED LECTURE IN BIOLOGICAL ENGINEERING\n(sandwiches served)\n\nAbstr
 act:\nProtein design—that is\, the construction of entirely new protein 
 sequences that fold into prescribed structures—has come of age.  It is 
 now possible to design proteins de novo using simple rules of thumb or com
 putational design methods.  The designs can be made rapidly via peptide s
 ynthesis or the expression of synthetic genes\; and the resulting proteins
  can usually be characterised all the way through to high-resolution X-ray
  crystal structures.  Contemporary questions in the protein-design field 
 include: What do with these new-found skills?  What protein structures an
 d functions do we target?  How far can we move past the confines of natur
 al protein structures and functions?  And\, how do we make protein design
  accessible to all\, including non-specialists interested in tackling real
 -life biological and technological problems?\n \nThis talk will address t
 hese questions with reference to simple through to complex and functional 
 protein designs that we have explored over the past 5 – 10 years.  Thes
 e use a straightforward protein structure\, called the alpha-helical coile
 d coil\, which are bundles of 2 or more alpha helices found in many protei
 n-protein interactions.  As such it provides an excellent basis for build
 ing proteins from the bottom up.\n \nThe vast majority of coiled-coil des
 igns have been based on simple rules of thumb learnt from natural proteins
  or derived empirically through experiment.1 These rules relate sequence t
 o structure to guide the specification of coiled-coil oligomerization stat
 e\, strand orientation\, partner selection\, and\, to some extent\, stabil
 ity.  This has been extremely informative and productive\, and design and
  engineering is probably more advanced for coiled coils than for any other
  protein structure.2 However\, to move past the low-hanging fruit of coile
 d-coil design\, and into the so-called dark matter of protein structures\,
  we will all have to learn new tricks.  To address this we have begun to 
 tackle coiled-coil design parametrically using computational methods.3  W
 e have developed easy-to-use computational modelling tools4 and a more-sop
 histicated suite of programs called ISAMBARD5 that allow the rapid generat
 ion and optimisation of protein designs in silico.\n \nThe talk will desc
 ribe how a serendipitous discovery of a 6-stranded alpha-helical barrel6 l
 ed us to develop these computational methods\; and how we have used them t
 o deliver entirely new non-natural protein structures predictably.7 It wil
 l demonstrate the utility of this approach to make water-soluble protein-l
 ike barrels and pores\, which we have engineered to form materials\, bind 
 small molecules\, and catalyse simple reactions.8\,9 Most recently with th
 e Bayley lab (Oxford)\, we have engineered membrane-soluble variants of th
 ese alpha-helical barrels that insert into lipid bilayers and conduct ions
  in a voltage-dependent manner.10  The talk will touch on how the barrels
  and related structures are improving our general understanding of coiled 
 coils.\n \n1.    The design of coiled-coil structures and assemblies.
 \n       DN Woolfson.  Adv Prot Chem 70\, 79-112 (2005)\n2.    C
 oiled-coil design: updated and upgraded.\n       DN Woolfson. Subcel
 lular Biochemistry 82\, 35-61 (2017)\n3.    De novo protein design: how
  do we expand into the universe of possible protein structures?\n    
    DN Woolfson et al. Curr Opin Struct Biol 33\, 16-26 (2015)\n4.   CC
 Builder: an interactive web-based tool for building\, designing and assess
 ing coiled-coil-protein assemblies.\n      CW Wood et al. Bioinformat
 ics 30\, 3029-3035 (2014)\n5.   ISAMBARD: an open-source computational e
 nvironment for biomolecular analysis\, modelling and design\n      CW
  Wood et al. Bioinformatics In press (2017)\n6.   A de novo peptide hexa
 mer with a mutable channel.\n      NR Zaccai et al. Nature Chem Biol 
 7\, 935-941 (2011)\n7.   Computational design of water-soluble a-helical
  barrels.\n      AR Thomson et al.\, Science 346\, 485-488 (2014)\n8.
    Modular design of self-assembling peptide-based nanotubes.\n     
  NC Burgess et al. J Am Chem Soc 137\, 10554-10562 (2015)\n9.   Installi
 ng hydrolytic activity into a completely de novo protein framework.\n  
     AJ Burton et al.\, Nature Chem 8\, 837-844 (2016)\n10. A monodisper
 se a-helical peptide barrel.\n      KR Mahendran et al.\, Nature Chem
  9\, 411-419\, (2017)\n\n\nBio:\nProf. Dek Woolfson took his first degree 
 in Chemistry at the University of Oxford in 1987.  He then did a PhD at t
 he University of Cambridge followed by post-doctoral research at Universit
 y College London and the University of California\, Berkeley.  After 10 y
 ears as Lecturer through to Professor of Biochemistry at the University of
  Sussex\, he moved to the University of Bristol in 2005 to take up a joint
  chair in Chemistry and Biochemistry.  His research has always been at th
 e interface between chemistry and biology\, applying chemical methods and 
 principles to understand biological phenomena.  Specifically\, his group 
 is interested in the challenge of rational protein design\, how this can b
 e applied in synthetic biology and biotechnology\, and with a particular e
 mphasis on making completely new protein structures and functions\, and al
 so biomaterials for applications in biotechnology\, cell biology and medic
 ine.\nProf. Woolfson is Director of BrisSynBio\, a BBSRC/EPSRC-funded Synt
 hetic Biology Research Centre.\n\nLunch with the speaker after the talk (f
 or grad students and postdocs only): sign up here for one of nine slots (f
 irst come\, first served...).
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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