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The artificial cell: biology-inspired compartmentalisation of chemical function

Scientific meeting

Location

Kavli Royal Society Centre, Chicheley Hall, Newport Pagnell, Buckinghamshire, MK16 9JJ

Overview

Theo Murphy meeting organised by Dr Barbara Ciani, Dr Paul Beales and Professor Stephen Mann FRS

Computer Generated Imagery illustration of synthetic protocells. Credits: Supplied by Professor Oscar Ces, Imperial College London

This meeting brings together life and physical scientists to explore mechanisms of biological compartmentalisation and how these principles can be harnessed to develop smart technologies. We will address how repurposing of biological and synthetic components can be used to create artificial cells for development in areas such as fuel production, drug delivery and environmental remediation. 

Speaker biographies and talk abstracts will be available shortly. The draft schedule is available below.

Recorded audio of the presentations will be available on this page after the meeting has taken place. Meeting papers will be published in a future issue of Interface Focus.

Poster session

There will be a poster session on Monday 26 February 2018. If you would like to apply to present a poster please submit your proposed title, abstract (no more than 200 words and in third person), author list and name of the proposed presenter and institution to the Scientific Programmes team with the subject line "Poster submission: The artificial cell" by 15 January 2018. Please note that places are limited and are selected at the scientific organisers discretion. Poster abstracts will only be considered if the presenter is registered to attend the meeting.

Attending this event

This is a residential conference, which allows for increased discussion and networking

  • Free to attend
  • Advanced registration essential (please request an invite)
  • Catering and accommodation available to purchase during registration

Enquiries: contact the Scientific Programmes team.

Event organisers

Select an organiser for more information

Schedule of talks

26 February

09:00-12:00

Session 1

5 talks Show detail Hide detail

Chairs

Dr Barbara Ciani, University of Sheffield, UK

09:10-09:35 Navigating the endosome: the role of receptor ubiquitination and ubiquitin-binding adaptors

Professor Philip Woodman, University of Manchester, UK

Abstract

The endocytic pathway is the gateway between cells and their environment, and promotes diverse events such as nutrient uptake and cell migration. Membrane proteins (“cargoes”) enter endocytic vesicles and reach the endosome. From here they are recycled to the surface, or sorted to intralumenal vesicles (ILVs) to generate a multivesicular body (MVB) en route to the lysosome. The generation of transport intermediates at all points of the endocytic pathway involves the ordered recruitment of an array of membrane-sculpting adaptor proteins, which recognise cargo and coordinate the local induction of membrane curvature. The impairment of these adaptor proteins, or their defective regulation, gives rise to errors in compartmentalisation. One class of endocytic cargo that is transported to the MVB is exemplified by the epidermal growth factor receptor (EGFR). For these cargoes, the sorting signal is generated by receptor ubiquitination, a reversible post-translational modification. A broad range of ubiquitin-binding adaptor proteins recognise ubiquitinated cargoes and promote their endocytic sorting. These adaptors themselves are regulated by reversible ubiquitination, generating a network of ubiquitin homeostasis that governs endocytic trafficking. The key regulators of this network, ubiquitin ligases and deubiquitinating enzymes, must also coordinate their functions with membrane curvature.

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09:45-10:10 Decision making in autophagy – How to loose specificity

Dr Thomas Wollert, Institut Pasteur, France

Abstract

Autophagy is a pivotal recycling pathway that operates in all eukaryotic cells. More than 40 AuTophaGy related (Atg) proteins are known in yeast and many of them are conserved in humans. In non-stressed, vegetative cells, autophagy mainly recycles unwanted or damaged cytoplasmic components by exclusively engulfing them into autophagic membrane sacks, termed phagophores. In stressed cells, however, autophagy loses its selectivity and degrades bulk cytoplasm. The regulation of this dramatic loss in selectivity is intimately intertwined with the onset of human diseases such as neurodegeneration or cancer. Its molecular bases remained, however, not well understood. Through a combination of classical biochemistry and cell biology with cutting edge in vitro reconstitutions, Dr Wollert and colleagues have been able to solve the long standing question how selectivity is regulated at a molecular level in yeast. They found that the decision is made at the earliest step in autophagy, i.e. nucleation of the phagophore.

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10:20-10:50 Coffee

10:50-11:15 Compartmentalisation and crowding in artificial membranes

Professor Mark Wallace, King's College London, UK

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11:25-11:50 Mimicking membrane scission in vitro

Professor Patricia Bassereau, Institut Curie, France

Abstract

Eukariotic cells are highly compartmentalized to achieve local special functions, but nevertheless have to exchange lipids and proteins between compartments and with the exterior of the cell. Thus, traffic intermediates (vesicles, tubules) have to be formed and detached from donor membranes to be transported and deliver their cargos and membrane to an acceptor compartment. Cell compartmentalization thus works hand-in-hand with membrane scission to allow for these exchanges. Reconstituted membrane systems have been instrumental to reveal mechanisms that drive membrane scission of bud neck in vivo, such as constriction by the ATPase dynamin involved in endocytosis or by line tension at the edge of membrane domains. Reconstitution approaches have similarly allowed recently to reveal a new scission mechanism, not based on constriction but on the friction between a protein scaffold and the membrane that produces a viscoelastic-like response and a scission when membrane tension exceeds lysis tension: Friction-Driven Scission (FDS). Professor Bassereau will show how this mechanism was shown using a combination of reconstituted systems and theoretical modelling.

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12:00-14:10

Lunch

14:10-17:00

Session 2

5 talks Show detail Hide detail

Chairs

Professor Stephen Mann FRS, University of Bristol, UK

14:10-14:35 Adaptive compartments with life-like behaviour

Professor Jan Van Hest, Technische Universiteit Eindhoven, The Netherlands

Abstract

Compartmentalization is generally regarded as one of the key prerequisites for life. In living cells, not only the cell itself is a compartment, with its properties controlled by the semipermeable cell membrane, but also the organelles play a crucial role in protecting and controlling biological processes. To better understand the role of compartmentalization, there is clear need for model systems that can be adapted in a highly controlled fashion, and in which life-like properties can be installed. Polymer-based compartments are robust and chemically versatile, and as such are a useful platform for the development of life-like compartments. In this contribution both an artificial organelle and cell system will be discussed. The artificial organelles are composed of biodegradable amphiphilic block copolymers that self-assemble into vesicular structures. These so-called polymersomes are loaded with enzymes and are semi-permeable for small molecule substrates. Upon introduction in living cells, they affect metabolic pathways as artificial organelles. A different type of polymersome is created via a shape change process in which a bowl-shaped structure is obtained. Within the cavity of the bowl enzymes are loaded which provide the nanostructure with motility upon conversion of chemical energy into kinetic energy. The synthetic cell platform is composed of a complex polymer coacervate, stabilized by a biodegradable block copolymer. The specific feature of the polymer membrane is its semipermeable character. Enzymes inside the protocell can therefore still be reached by their substrates, and small molecule products can be excreted. This allows protocell communication with this robust synthetic platform.

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14:45-15:10 Biomimetic synthesis of artificial magnetosomes

Dr Sarah Staniland, University of Sheffield, UK

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15:20-15:50 Tea

15:50-16:15 Model systems for membraneless subcellular organelles: Compartmentalization of biomolecules and reactions by liquid-liquid phase coexistence

Professor Christine Keating, Penn State University, USA

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16:25-16:50 Protein design in the cell: towards a synthetic proteome

Professor Dek Woolfson, University of Bristol, UK

Abstract

Protein 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 computational design methods. The designs can be made rapidly via peptide synthesis 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 we do with these new-found skills? What protein structures and functions do we target? How far can we move past the confines of natural protein structures and functions? And, how can we take protein design from an exercise largely done in silico and in vitro into a truly synthetic biology and take it in vivo? This talk will address these questions with reference to simple through to complex and functional protein designs that we have explored over the past 5–10 years. These use a straightforward protein structure, called the alpha-helical coiled coil, which are bundles of 2 or more alpha helices found in many protein-protein interactions. As such it provides an excellent basis for building proteins from the bottom up. The vast majority of coiled-coil designs have been based on simple rules of thumb learnt from natural proteins or derived empirically through experiment. These rules relate sequence to structure to guide the specification of coiled-coil oligomerization state, strand orientation, partner selection, and, to some extent, stability. This has been extremely informative and productive, and design and engineering is probably more advanced for coiled coils than for any other protein structure. However, to move past the low-hanging fruit of coiled-coil design, and into the so-called dark matter of protein structures, we will all have to learn new tricks. To address this Professor Woolfson has begun to tackle coiled-coil design parametrically using computational methods. Professor Woolfson has developed easy-to-use computational modelling tools and a more-sophisticated suite of programs called ISAMBARD that allow the rapid generation and optimisation of protein designs in silico. The first part of the talk will describe how a serendipitous discovery of a 6-stranded alpha-helical barrel led his group to develop these computational methods, and how they have used these to deliver entirely new non-natural protein structures predictably. It will show the utility of this approach to make water-soluble protein-like barrels, which the group has engineered to form materials, bind small molecules, and catalyse simple reactions. Secondly, Professor Woolfson will demonstrate how we might take protein design in vivo with recent work with the Warren lab (Kent) and the Verkade lab (Bristol). He has engineered hybrids of a de novo heterodimer and a natural component of bacterial microcompartments. When expressed in E. coli, the hybrid assemblies to form a cytoscaffold that permeates the cells, and can act as a support for the co-localisation of functional enzymes.

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17:00-18:00

Poster session

27 February

09:00-12:25

Session 3

5 talks Show detail Hide detail

Chairs

Professor Oscar Ces, Imperial College London, UK

09:00-09:25 Regenerating the nuclear envelope during exit from mitosis

Dr Jeremy Carlton, KCL and Francis Crick Institute, UK

Abstract

During cell division, as well as separating their duplicated genomes, cells must also deconstruct, separate and then reconstruct many of their cytoplasmic organelles.  Mammalian nuclei are surrounded by a double-membraned organelle called the nuclear envelope that is continuous with the endoplasmic reticulum. During mitotic exit, sheets of ER envelope the forming daughter nuclei and become fused together to generate a sealed nuclear envelope. In addition to its role in membrane abscission during cytokinesis, viral budding, endosomal sorting and plasma membrane repair, the endosomal sorting complex required for transport-III (ESCRT-III) machinery has recently been shown to participate in nuclear envelope sealing during mitotic exit. Nuclear envelope localisation of ESCRT-III is dependent upon the ESCRT-III component CHMP7 and the inner nuclear membrane protein LEM2. However, it is unclear how ESCRT-III actually engages nuclear membranes. Here, Dr Carlton shows that the N-terminus of CHMP7 acts as a novel membrane-binding module. This membrane-binding ability allows CHMP7 to bind to the endoplasmic reticulum (ER), an organelle continuous with the NE, and provides a platform to direct NE-recruitment of ESCRT-III during mitotic exit. Dr Carlton also identifies novel activities in the C-terminus of CHMP7 that restrict its activity to the inner-nuclear membrane and help us understand how this complex can help regenerate the nucleus. Dr Carlton finds that mutations that compromise CHMP7 function also prevent assembly of downstream ESCRT-III components at the reforming NE and proper establishment of post-mitotic nucleo-cytoplasmic compartmentalisation. These data identify a novel membrane-binding activity within an ESCRT-III subunit that is essential for post-mitotic nuclear regeneration.

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09:35-10:00 Bottom-up assembly of a minimal divisome

Professor Petra Schwille, Max Planck Institute of Biochemistry, Germany

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10:40-11:05 Buckling of an epithelium growing under spherical confinement

Dr Aurelien Roux, University of Geneva, Switzerland

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11:15-11:40 Signalling reactions on membrane surfaces: the roles of space, force, and time

Professor Jay Groves, University of California, Berkeley, USA

Abstract

Most intracellular signal transduction reactions take place on the membrane. The membrane provides much more than just a surface environment on which signalling molecules are concentrated. There is a growing realization that multiple physical and chemical mechanisms allow the membrane to actively participate in the signalling reactions. Using a combination of single molecule imaging and spectroscopic techniques, Professor Jay Groves’ research seeks to directly resolve the actual mechanics of signalling reactions on membrane surfaces both in reconstituted systems and in living cells. These observations are revealing new insights into cellular signalling processes as well as some unexpected functional behaviours of proteins on the membrane surface. The Groves’ lab has recently discovered a type of signalling reaction phenomenon that enables geometrical features of the membrane surface to couple directly to the outcome of a signalling process.

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11:50-12:15 Harnessing Nature's ability to create membrane compartmentalisation

Dr Paul Beales, University of Leeds, UK
Dr Barbara Ciani, University of Sheffield, UK

Abstract

A biological cell can be thought of as a complex chemical reactor where vast numbers of interactions are simultaneously taking place. To prevent unwanted cross-talk and interference within the ‘noise’ of all these concurrent chemical pathways, a cell compartmentalises these processes localizing different functions within individual membrane-bound structures (organelles). Confinement of chemical processes also allows a cell to maintain incompatible environments that are optimal for each organelle's function, which would not be possible within a single ‘pot’. If we are to mimic this complexity within synthetic ‘nanoreactors’, we need to develop ways of mimicking cellular compartmentalisation within synthetic structures. Here, Dr Barbara Ciani and Dr Paul Beales will show that it is possible to create multi-compartment architectures, in vitro, using a purified membrane remodelling protein complex. Barbara and Paul will also show how this in vitro system allows us to learn what controls the membrane shaping action of these proteins and therefore regulate the encapsulation of cargo.

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12:25-13:45

Lunch

13:45-16:30

Session 4

5 talks Show detail Hide detail

Chairs

Dr Paul Beales, University of Leeds, UK

13:45-14:10 A cellular transition to evolutionary dynamics

Professor Lee Cronin, University of Glasgow, UK

Abstract

Complex chemical systems contain not only diverse chemistry, but also couple molecular processes to the environment via dynamical interactions. Whereas the formation of dissipative chemical fluxes in polymer systems, soft materials, or inorganic crystal gardens are controlled by macroscopic dynamics that can be fine-grained, the exploration of the development of complexity at the molecular level has not been widely explored.  In this talk Professor Cronin will present his group’s research in this area that aims to drive the development of complexity in molecular systems by coupling them to non-equilibrium dynamics associated with proto-cell systems. The ultimate aim is to explore how evolutionary dynamics and complex molecular machinery might emerge giving a new avenue for the design of molecular machines and autonomous life-like systems. To explore this Professor Cronin has developed a series of fully autonomous chemical robots aim to look at flows, proto-cells, and self-replicating chemistry.

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14:20-14:45 Microfluidic technologies for the bottom-up construction of artificial cells

Professor Oscar Ces, Imperial College London, UK

Abstract

This talk will outline microfluidic strategies for bottom-up synthetic biology that are being used to construct multi-compartment artificial cells where the contents and connectivity of each compartment can be controlled. These compartments are separated by biologically functional membranes that can facilitate transport between the compartments themselves and between the compartments and external environment. These technologies have enabled us to engineer multi-step enzymatic signalling cascades into the cells leading to in-situ chemical synthesis and systems that are capable of sensing and responding to their environment. In addition, we have developed hybrid systems fusing living and non-living components to generate higher order systems. Finally, this talk will provide an overview of microfluidic single cell analysis tools for counting the protein copy number in single cells and artificial cells.

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14:55-15:25 Tea

15:25-15:50 Collective behaviour in synthetic protocell communities

Professor Stephen Mann FRS, University of Bristol, UK

Abstract

Recent progress in the chemical construction of micro-compartmentalized colloidal objects comprising integrated biomimetic functions is paving the way towards rudimentary forms of artificial cell-like entities (protocells) for modelling complex biological systems, exploring the origin of life, and advancing future proto-living technologies. Although several new types of protocells are currently available, the design of synthetic protocell communities and investigation of their collective properties has received little attention. In this talk, Professor Mann reviews some recent experiments undertaken in his laboratory that demonstrate simple forms of higher-order dynamic behaviour in synthetic protocells. Professor Mann will discuss four new areas of investigation: (i) enzyme-powered motility and collective migration in buoyant organoclay/DNA protocells; (ii) artificial predatory behaviour in mixed populations of proteinosomes and coacervate micro-droplets; and (iii) artificial phagocytosis behaviour in a binary population of magnetic and silica colloidosomes. He will use these new model systems to discuss pathways towards chemical cognition, modulated reactivity, basic signalling pathways and non-equilibrium activation in compartmentalized artificial micro-ensembles.

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16:00-16:30 Final discussion/Overview

The artificial cell: biology-inspired compartmentalisation of chemical function Kavli Royal Society Centre, Chicheley Hall Newport Pagnell Buckinghamshire MK16 9JJ