Native nanodiscs preserve membrane:protein assemblies (memteins) for structure-function analysis and have changed the established landscape of research into cellular membranes, as there is no other scalable method for their isolation.
By allowing membrane proteins to be purified and studied while retaining their assymmetric biological lipid environment, synthetic polymers including SMA, PMA and DIBMA enable the study of lipid intact membrane complexes by methods including cryoEM, and new polymer derivatives are emerging for wider applications including native mass spectrometry and drug molecule screening.
This meeting will explore the latest developments within the field, bringing together a wide range of researchers to share their findings and to develop conceptual advances including lipidons that represent lipid codes, PIP-stops and MET-stops which regulate membrane recognition, and mechanisms of lipid-bound machines.
Our next webconference is on June 15, 2023. Please also pencil in our in-person International SMALP conference in Knoxville, TN from Oct 19-21, 2023.
Speakers on June 15 include:
9:00 am MDT Kunyu Wang, a student with Youdong Mao at State Key Laboratory for Mesoscopic Physics, School of Physics and Peking-Tsinghua Joint Center for Life Science, Peking University, Beijing, and recently published Asymmetric conformations of cleaved HIV-1 envelope glycoprotein trimers in styrene-maleic acid lipid nanoparticles in Commun Biol.
9:20 am Kirill Nadezhdin Postdoctoral Scientist and previously graduate student at Columbia University Irving Medical Center, who recently published on the structural mechanisms of TRPM7 activation and inhibition in Nature Communications.
9:40 am break
9:45 am Willem Kegel, Professor Science Chemistry, Debye Institute for Nanomaterials Science Physical and Colloid Chemistry, University of Utrecht, who recently published on cooperative transitions involving hydrophobic polyelectrolytes such as polymers including SMA interacting with membranes in PNAS.
10:05 am Luis Real Hernandez, PhD Student, University of Virginia has recently published Lipid packing is disrupted in copolymeric nanodiscs compared with intact membranes in the Biophys J.
10:25 break
10:30 am David Swainsbury, Lecturer in Biochemistry at University of East Anglia, cyclist and unapologetic Trekkie, who recently published on the cryo-EM structure of the four-subunit Rhodobacter sphaeroides cytochrome bc1 complex in styrene maleic acid nanodiscsin PNAS.
10:50 am Piotr Koprowski, Assistant Professor, Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology PAS (Poland) who recently published on pharmacological characterization of mitochondrial ROMK2 potassium channels in lipid bilayers.
11:10 am Moitrayee Bhattacharyya, Assistant Professor of Pharmacology, Yale University, who recently published on the determination of oligomeric organization of membrane proteins from native membranes at nanoscale-spatial and single-molecule resolution.
SMALP Conference Video for March 9, 2023
Program:
8:45 am Tips and Tricks session to share practical advice and ask any question
Session 1 Chair: Gestél Kuyler, PhD Student, Stellenbosch University & Coventry University
9:00 am Lukas Spantzel, PhD student with Michael Boersch, Jena University will speak on monitoring oligomerization dynamics of individual human neurotensin receptors in living cells and in SMALP nanodiscs, based on studies which are in press in PLOS One.
9:20 am Lena Bauernhofer, M.Sc. student with Sandro Keller, Institute of Molecular Biosciences (IMB), University of Graz is using native membrane-protein libraries and microfluidic diffusional sizing and will speak about measuring the cellular copy number and antibody affinity of an oncoprotein in a native lipid-bilayer environment.
9:40 am John Young, postdoc with Carol Robinson, University of Oxford will speak on Quantifying receptor-ligand interactions using Mass Photometry, and previously studied the outer membrane proteome of bacteria by mass spectrometry using peptidiscs.
10:00 Break for Q&A
Session 2 Chair: Valentina Corradi, Research Associate, Biocomputing, University of Calgary
10:05 am Ali Rasouli, PhD student with Emad Tajkhorshid, University of Illinois at Urbana Champaign on Differential dynamics and direct interaction of bound ligands with lipids in multidrug transporters as reported in PNAS USA.
10:25 am Sudhir Sinha, Emeritus Scientist, Department of Clinical Immunology and Rheumatology, Postgraduate Institute of Medical Sciences, India, will speak on characterisation of SMALPs prepared from Mycobacterium tuberculosis plasma membrane in pursuit of a nanoparticle-based vaccine against tuberculosis.
10:45 am Ronnie Fang, Assistant Professor of Pediatrics at UC San Diego, and led the cellular nanodisc research effort that was recently published in ACS Nano on Cellular Nanodiscs Made from Bacterial Outer Membrane as a Platform for Antibacterial Vaccination.
11:05 Break for Q&A
Session 3 Chair: Rakesh Bhat, Research Scientist, Department of Biochemistry, University of Alberta
11:10 am Rhythm Shukla, PhD student with Markus Weingarth at the Department of NMR Spectroscopy and Membrane Biophysics, University of Utrecht, and recently published Teixobactin kills bacteria by a two-pronged attack on the cell envelope in Nature.
11:30 am Michael Overduin, Professor, Dept of Biochemistry, University of Alberta on using COMPOSEL to classify proteins such as transmembrane membrane readers and membrane-binding by SARS-CoV-2 variant spike proteins.
11:50 Discussion and close
Testimonial: "The SMALP meetings have really been my favorite pandemic Zoom series - I learn something new each meeting, there are lots of interesting questions, and atmosphere is always friendly and welcoming." - attendee
International SMALP Conference on Dec. 8, 2022
Session 1 chaired by Sandro Keller, Karl-Franzens-Universität Graz
9:00 Alba Torrents de la Peña, postdoctoral fellow with Andrew Ward at The Scripps Research Institute, previously a PhD student at the AMC - Academic Medical Centerrecently published the structure of the hepatitis C virus E1E2 glycoprotein complex in Science.
9:20 Maria Falzone, Postdoctoral Researcher, The Rockefeller University with Alessio Accardi, previously at Weill Cornell Graduate School of Medical Sciences and (PhD) and Drew University (BSc); recently published TMEM16 scramblases thin the membrane to enable lipid scrambling in Nat Commun. Slides
9:40 Philipp Hanisch, Postdoc at Cube Biotech involved in research and development of its membrane protein services, previously at Heinrich-Heine-Universität Düsseldorf, will present PolyHunter: Introducing a new matrix to deplete free copolymer from membrane protein solubilizate.
10:00 Open Discussion / break
Session 2 chaired by Bert Klumperman, Stellenbosch University
10:05 Henriette Autzen, Associate Professor, Biomolecular Sciences, Department of Biology, University of Copenhagen, focuses on molecular dynamics simulations, protein crystallization and single-particle cryo-electron microscopy, and recently published on characterization of divalent cation interactions with AASTY native nanodiscs in ACS Appl. Polym. Mater.
10:25 David Glück, PhD Student, Karl-Franzens-Universität Graz with Sandro Keller, will present Electroneutral polymer nanodiscs enable interference-free probing of membrane proteins in a lipid-bilayer environment, was published in Small. Slides
10:45 Open Discussion / break
Session 3 chaired by Johanna Syrjanen, Cold Spring Harbor Laboratory
10:50 Melina Daniilidis is a PhD Student in Franz Hagn's Lab of Structural Membrane Biochemistry Bavarian NMR Center, Technical University of Munich, and will present Circularized MSP nanodiscs facilitate high-resolution NMR studies of membrane proteins and recently published on a paper on this topic in J Mol Biol.
11:10 Katia Cosentino, Junior Professor, Molecular Cell Biophysics, Universität Osnabrück, aims to understand the molecular mechanisms of membrane pore formation, and recently published on the interplay between BAX and BAK tunes apoptotic pore growth to control mitochondrial-DNA-mediated inflammation in Mol Cell.
11:30 Open Discussion / break
Session 4 chaired by Debbie Hansen, Arizona State University
11:35 Wei Mi, Assistant Professor, Department of Pharmacology at Yale University School of Medicine, Yale University uses methods including cryoEM to study membrane proteins and recently published on the regulatory mechanisms of lipopolysaccharide synthesis in Escherichia coli in Nat Comms.
11:55 Alexander Nevzorov, Professor, Department of Chemistry, North Carolina State University, focuses on structure determination of membrane proteins, and recently published on aligned peptoid-based macrodiscs for structural studies of membrane proteins by oriented-sample NMR in Biophys J.
12:15 pm MDT Closing Discussions
International SMALP Conference on Sept 15, 2022
Benedict Dirnberger is a Postdoc with Kathryn Lilley, Department of Biochemistry, University of Cambridge, and recently published Drosophila nicotinic acetylcholine receptor subunits and their native interactions with insecticidal peptide toxins in Elife. (9:00 am MDT)
Harris Bernstein, Section Chief: Protein Biogenesis Section, Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) will give a talk entitled Using SMALPs to obtain insights into the assembly of bacterial outer membrane proteins. (9:20 am MDT)
Gestél Kuyler, PhD Student, Department of Chemistry and Polymer Science, Stellenbosch University & Centre for Sports, Exercise and Life Sciences, Coventry University: Novel terpolymers for detergent-free solubilisation of GPCRs. (9:40 am MDT)
Emma Gordon, PhD student with Gary Lorigan at the Department of Chemistry and Biochemistry, Miami University, and recently published Formation of styrene maleic acid lipid nanoparticles (SMALPs) using SMA thin film on a substrate in Analytical Biochem. (10:05 am MDT)
Johanna Syrjanen, Postdoc with Hiro Furukawa at Keck Structural Biology, Cold Spring Harbor Laboratory with will speak on Using nanodiscs as a tool to define the structure and function of large pore channels, and recently published Structure and assembly of calcium homeostasis modulator proteins in Nature Struct Mol Biol. (10:25 am MDT)
Krishnarjuna Bankala, Postdoc with Ayyalusamy Ramamoorthy, University of Michigan, who recently published on direct extraction of membrane proteins using SMA-based and inulin-based polymers including "Detergent-free isolation of CYP450-reductase's FMN-binding domain in E. coli lipid-nanodiscs using a charge-free polymer" Chem Commun. 58:4913-491. (10:45 am MDT)
Youzhong Guo, Assistant Professor of Medicinal Chemistry, Department of Medicinal Chemistry, Institute for Structural Biology, Drug Discovery and Development VCU, School of Pharmacy will give a talk entitled Advances of Native Cell Membrane Nanoparticles System. (11:10 am MDT)
Michael Marty, Associate Professor Department of Chemistry & Biochemistry, The University of Arizona applies noncovalent or native mass spectrometry to study the structures and biophysics of peptides and proteins in membrane environoments, and will speak about Using mass spectrometry to study interactions of membrane proteins in nanodiscs. (11:30 am MDT)
Rajan Lamichhane, Assistant Professor, Department of Biochemistry & Cellular and Molecular Biology, The University of Tennessee at Knoxville focuses on conformational dynamics of biomolecular interactions, and will present Single-molecule view of the human A2A adenosine receptor dynamics in a native-like environment. (11:50 am MDT)
European SMALP Conference 2022 (Apr 6-8)
Speakers included:
Adrian Kopf, Utrecht University: Synthesis and evaluation of a novel library of copolymers: Expanding the toolbox for the study of membrane proteins
Antoinette Killian, Utrecht University, The Netherlands
Bert Klumperman, Stellenbosch University: Non-alternating SMA with narrow molecular weight distribution
David Roper: University of Warwick: SMALP isolation of the S.pneumoniae FtsEX divisome complex with peptidoglycan hydrolase PcsB and actin homologue FtsA, required for cell division.
George Neville - University of Bath: Fluorescent SMA copolymers to facilitate membrane protein studies in lipid nanodiscs
Steven Harborne, Peak Proteins: Preparation of GPCRs in SMALP for Biophysical Characterisation
Isabelle Mouro-Chanteloup, Inserm: Detergent-free isolation of native red blood cell membrane complexes
James Mitchell-White, University of Nottingham: A fluorescent inhibitor for probing substrate binding to ABCG2
Jan Kubicek, Cube-Biotech: Finding the perfect match- utilizing shotgun proteomics to create a global database of membrane protein solubilisation
John Young, University of Oxford: Combining Peptidiscs and Mass Photometry to characterize membrane proteins in aqueous solution
Laura Wilk, Robert Koch Institute: Mimicking the multivalent binding of bacterial protein toxins to their cellular receptors in a native-like membrane environment
Mark Wheatley, Coventry University
Michael Overduin, University of Alberta: SMALP technology and new concepts for membrane targeted drug discovery
Paula Booth, Kings College London: Co-translational membrane protein folding in native lipid environments
Peter Judge, University of Oxford
Rachel Grime, University of Birmingham
Rosa Catania, University of Leeds: Detergent-free reconstitution of membrane proteins into hybrid polymer-lipid vesicles
Stephanie Nestorow, University of Birmingham: Polymer Nanoencapsulation Techniques as a Tool to Investigate Insecticide Targets
Stephen Hall, University of Warwick, UK
Tim Dafforn, University of Birmingham
Xueqing Wang, University of Birmingham: Characterising platelet membrane receptors using SMALPs
A workshop on membrane protein solubilization, purification and downstream characterization using native nanodiscs is included from 9:00-12:30 on April 8.
This conference is being organized by the Biochemical Society with sponsors including Biochemical Society Transactions, Nanotemper, Cube Biotech, Cytiva,Generon , Molecular Dimensions, and Orbiscope. Bursaries are available.
The UK workshop on membrane proteins covering solubilization and biophysical characterization techniques will be held at Aston University from April 4-6, 2022 with talks by:
Alan Goddard, Alice Rothnie, Megan Cox, Vincent Postis: Lipid nanoparticles
Alice Rothnie, Aston University: Lipid nanoparticles (SMALPs)
Andrew Quigley, Diamond Light Source: High throughput membrane protein expression and purification
Bonnie Wallace, Birkbeck: Circular dichroism of membrane proteins
Boyan Bonev, University of Nottingham: NMR of membrane proteins
Colin Grant, Refeyn: Mass Photometry: Measuring Molecules with Light
Corinne Spickett, Aston University: Mass spec - lipidomics
Isabel Moraes, NPL: Membrane protein crystallography
John Simms, Aston University: MD of membrane proteins
Luke Clifton, STFC: Unravelling the Structural Complexity of Protein-Lipid Interactions with Neutron Reflectometry
Marcus Allen, University of Brighton: Ion channel recording in planar lipid bilayers
Megan Cox, Aston University/Meritics Ltd: Nanoparticle analysis
Stephen Muench, University of Leeds: Single particle CryoEM for membrane protein structure
Vincent Postis, University of Leeds: Membrane protein solubilisation: detergents, SMALPs, nanodiscs and amphipols
International SMALP Conference on January 28, 2022
8:45 Tips & Tricks to share insights into how to use amphipathic polymers and nanodiscs
Session 1 Chair: Bert Klumperman, Stellenbosch University
09:00 Annette Meister, Institute for Biochemistry and Biotechnology, Martin Luther University Halle-Wittenberg studies membrane protein interactions and nanodiscs and published Solubilization of artificial mitochondrial membranes by amphiphilic copolymers of different charge and Nanoscale Model System for the Human Myelin Sheath.
09:20 Dmitry Veprintsev, Professor of Molecular and Cellular Pharmacology, Centre of Membrane Proteins and Receptors (COMPARE), University of Nottingham is developing approaches for incorporation of protein and systems dynamics of GPCRs into drug discovery, and published Functional solubilization of the β2-adrenoceptor using diisobutylene maleic acid.
09:40 Xueqing Wang, PhD student in University of Birmingham, UK, will present "Characterising platelet membrane receptors in their native environment using SMALP" and focuses on the investigation of a wide range of platelet membrane receptor interactions and stoichiometry using SMALP-related assays, and the purification of SMALPs containing platelet collagen receptor GPVI from over-expression systems.
Session 2 Chair: Brittany Wiseman, University of Alberta
10:05 Bernadette Byrne, Professor of Molecular Membrane Biology, Faculty of Natural Sciences, Department of Life Sciences, Imperial College London studies the structures, lipid interactions and aggregation properties of membrane proteins, and develops tools and amphilies for large- scale production of stable, functional membrane proteins for structural biological characterization.
SLIDES
10:25 Benoît Zuber, Associate Professor for Anatomy and Structural Biology, University of Bern, studies synaptic vesicles, neuronal signaling and exocytic mechanisms using cryo-electron microscopy and cryo-electron tomography, and published Cryo-EM structure of the octameric pore of Clostridium perfringens β-toxin.
10:45 Thorsten Schmidt, Assistant Professor for Experimental Biophysics Kent State University, is developing DNA-based tools and devices for single-molecule cryo-EM of membrane proteins as well as other applications in biophysics, molecular biology, nano photonics he spoke on DNA-encircled lipid nanodiscs. SLIDES
Session 3 Chair: Stephanie Pitch, UC Santa Cruz
11:10 Peter Tieleman, University of Calgary will speak on Analyzing lipid-protein interactions around GPCRs and focuses on biological membranes and molecular dynamics simulation methods for nanodiscs and membrane systems, analysis of interactions within proteins and lipids, and the development of improved lipid models.
11:30 Shijian Zhang, Instructor, Harvard Medical School and Department of Microbiology, Dana-Farber Cancer Institute will present HIV-1 envelope glycoproteins in SMALP are stable and preserve native conformations, and published Analysis of glycosylation and disulfide bonding of wild-type SARS-CoV-2 spike glycoprotein.
11:50 Pramod Kumar, Research Investigator at Cold Spring Harbor Laboratory and Post Doc Research Associate, University of Illinois at Urbana-Champaign, is using cryo-EM and SMALPs to better understand ion channel structure & dynamics; he published Structure and function at the lipid-protein interface of a pentameric ligand-gated ion channel.
Background on SMALP
The SMALP system is being developed by the international research community as an alternative to conventional detergents, which tend to dissociate, destabilize and deactivate native membrane proteins.
A variety of amphipathic polymers like styrene maleic anhydride have been found to directly and spontaneously solubilize proteins and bound lipids from membranes when activated. This provides opportunities for understanding and exploiting the structure and function of native membrane protein complexes.
As SMALP technology is relatively new, the participation of the wider community and sharing of new ideas and practices amongst researchers is the best way to ensure continued rapid development of the field.
Join our network and come to our meetings to discover how SMALP materials and methods could be used in your research.
Join our community.
The SMALP network offers polymers, methods and meetings to support the growing community of scientists and companies interested in the preparation of membrane nanodiscs formed by polymers including styrene maleic acid for biological research and drug discovery applications.
Register for a day of insightful talks from experts in the structural biology and functions of membrane proteins and nanodisc development, discussions with academic and industry leaders, and enjoy breakfast, lunch and coffee breaks on us.
These events are offered to bring together academic and industry experts, postdocs and students who are interested in membrane protein structural biology, lipidomics, proteomics, target discovery and biophysical analysis of bilayers and amphipathic polymers.
We welcome researchers from across academia and industry to join us in lively discussions and debate about the latest advances in native nanodiscs, membrane proteins, polymer chemistry, lipid biophysics, structural biology, and applications including drug discovery and delivery.