Skip to content

Overview

Scientific discussion meeting organised by Dr Yuval Elani, Dr David Lunn, Professor Thomas McLeish FRS, Dr Annela Seddon, Dr Tom Ellis, and Professor John Seddon.

This meeting will explore the emerging area of artificial cell science. Specifically, bottom-up synthetic biology approaches will be discussed, where molecular building blocks are brought together to yield protocells that mimic properties of biological systems. Biomimetic assemblies that traverse lengthscales (from sub-cellular structures to proto-tissues) will be covered. There will be a focus on potential applications of this research area.

Speaker biographies and the schedule of talks will be available soon. Speaker abstracts will be available closer to the meeting date. Recordings 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 an in person poster session on Monday 7 November at the meeting venue and an online poster gallery for the duration of the meeting. If you would like to apply to present a poster please submit your proposed title, abstract (not more than 200 words and in third person), author list, name of the proposed presenter and institution to the Scientific Programmes team no later than Monday 26 September 2022. Please include the text 'Poster abstract submission' in the email subject line. Please note that places are limited and posters are selected at the scientific organisers' discretion.

Attending this event

This meeting is intended for researchers in relevant fields.

  • Free to attend
  • Both in-person and online attendance will be available
  • Limited places, advance registration essential (more information about registration will be available soon)

Enquiries: contact the Scientific Programmes team

Organisers

Schedule

09:05-09:35
Synthetic cells: De novo engineering with DNA nanotechnology

Abstract

Can we construct a cell from non-living matter? In search for answers, bottom-up synthetic biology has successfully encapsulated functional sets of biomolecules inside lipid vesicles, yet a “living” synthetic cell remains unattained. Instead of relying exclusively on biological building blocks, the integration of new tools can be a shortcut towards the assembly of active and eventually fully functional synthetic cells. This is especially apparent when considering recent advances in DNA nanotechnology. DNA nanotechnology allowed us to engineer various functional parts for synthetic cells, which, meanwhile have found diverse applications as biophysical probes in cell biology. Recently, we engineered functional DNA-based mimics of a cytoskeleton. These cytoskeletons are capable of stimuli-responsive reversible assembly, cargo transport and can deform giant unilamellar lipid vesicles (GUVs) from within. We further demonstrate the division of GUVs based on phase separation or spontaneous curvture increase and osmosis rather than the biological building blocks of a cell’s division machinery. We derive a parameter-free analytical model which makes quantitative predictions that we verify experimentally. The osmolarity increase can be triggered by enzymatic reactions or by light-triggered release of caged compounds. Ultimately, by coupling GUV division to their informational content and their function, we aim for a prototype of a synthetic cell capable of evolution.

Speakers

09:35-09:50
Discussion
09:50-10:20

Abstract

Nucleic acid strand displacement involves the invasion of a double-stranded complex of nucleic acids (a DNA duplex, an RNA hairpin, etc.), by another DNA or RNA strand with an appropriate sequence. This process has been widely used in dynamic DNA nanotechnology and underlies the operation principle of many DNA-based molecular devices. Strand displacement reactions can be rationally designed and are therefore particularly attractive also for the realization of synthetic control circuits, with applications in molecular computing and synthetic biology alike. In this talk, several examples for such applications will be discussed, including switchable CRISPR/Cas systems, RNA-based sensors and circuits. We will also address challenges associated with the operation of strand displacement in complex environments and potential uses in the context of synthetic cells.

Speakers

10:20-10:35
Discussion
10:35-11:00
Coffee Break
11:00-11:30

Abstract

Abstract will be available soon
 

Speakers

11:30-11:45
Discussion
11:45-12:15

Abstract

Recently, artificial cell construction has been advancing at an accelerated pace. Artificial cells are autonomous molecular systems that mimic living cells. Artificial cells contribute to exploring soft matter properties of cell-like vesicular membranes and fluctuating biochemical reactions in vesicles. They also allow for the exploration of the origin of life by knowing the minimum physical elements for a cell. Furthermore, it is also expected to be applied to the construction of molecular robots that perform autonomous functions inside and outside the cell. These studies were triggered by computational methods to predict the structure and reactions of biomolecules on a large scale with high accuracy. Their molecular programmability will continue to play an essential role in the future. In this presentation, we report on droplet-based artificial cell studies based on the programming of DNA nanostructures. First, we present DNA droplets, which are liquid-liquid phase-separated droplets (coacervates) of DNA nanostructures. The static and dynamic properties of DNA droplets can be programmed by designing their base sequences. Second, DNA origami-based microcapsules are introduced. In general, artificial cellular vesicles are constructed by lipid membranes. Unlike lipid vesicles, DNA origami capsules have the potential that the physical properties of the membrane can be directly controlled through DNA nanostructure design. These systems will be applied to the material constructions for new cell-like molecular robots.

Speakers

12:15-12:30
Discussion
12:30-13:30
Lunch
13:30-14:00

Abstract

Abstract will be available soon
 

Speakers

14:00-14:15
Discussion
14:15-14:45
Toward autonomous “artificial cells” on a chip

Abstract

We study the assembly of programmable quasi-2D DNA compartments as “artificial cells” from the individual cellular level to multicellular communication. We will describe recent progress toward autonomous synthesis and assembly of cellular machines, synchrony, pattern formation, fuzzy decision-making, memory transactions, and electric field manipulation of gene expression.

Speakers

14:15-14:45
Discussion
15:00-15:30
Tea Break
15:30-16:00

Abstract

Abstract will be available soon
 

Speakers

16:00-16:15
Discussion
16:15-16:45

Abstract

Cell-free synthetic biology emerged as a viable in vitro alternative for biological network engineering. Cell-free synthetic biology implements biological systems in a coupled transcription – translation reaction and therefore is a well-defined environment that is easier to control and interrogate than complex cellular systems. I will discuss several technological and methodological advances including the development of microfluidic chemostat devices, a high-throughput microfluidic device, and a method to easily produce a recombinant cell-free system. With these tools we were able to rapidly prototype genetic networks and transplant them into living hosts and engineered gene regulatory networks from the bottom-up with synthetic Zinc-finger transcriptional regulators. More recently, we were able to demonstrate that it is possible to create a partially self-regenerating cell-free system that continuously produces up to seven essential proteins and does so for an extended period of time. This work lays the foundation for the development of a biochemical constructor and may ultimately enable the creation of a synthetic cell.

 

Speakers

16:45-17:00
Discussion
17:00-18:00
Poster Session
09:30-09:45
Discussion
09:00-09:30

Abstract

Biology is well equipped in exploiting a large number of out of equilibrium processes to support life. A complete understanding of these mechanisms is still in its infancy due to the complexity and number of the individual components involved in the reactions. However, a bottom up approach allows us to replicate key biological processes using a small number of basic building blocks. Moreover, this methodology has the added advantage that properties and characteristics of the artificial cell can be readily tuned and adapted. 

Here, I will present strategies for the design and synthesis of artificial cells based on hydrophobic effects such as lipid vesicles and proteinosomes and liquid-liquid phase separation of oppositely charged components (coacervates) and describe how these compartments may be used as platforms for implementing dynamic biological behaviour. 

Speakers

09:45-10:15
Mammalian cells and their interaction with artificial cells

Abstract

Bottom-up synthetic biology aims to substitute for missing/lost cellular activity or to add non-native function to mammalian cells and tissue. We focus on hydrogel-based artificial cells equipped with a specific life-like function, in particular, energy generation and cellular communication. 

The creation of self-sustaining systems require energy generation. In mammalian cells, mitochondria are responsible for the chemically driven adenosine triphosphate (ATP) synthesis. Here, mitochondria are used as a natural ATP producing subunit in hydrogel-based artificial cells. We co-encapsulated the ATP-dependent enzyme firefly luciferase with purified mitochondria to demonstrate the utilization of mitochondrially produced ATP in a cell-sized carrier, exemplified by the bioluminescent decarboxylation of D-luciferin. 

Collective behaviour in multicellular assemblies and on tissue level requires communication. Consequently, the integration of artificial cells with mammalian cells would benefit from supportive signal exchange between the artificial and natural entity. First, a one-way signal transfer is established by equipping two different types of artificial cells with catalytic function using metalloporphyrins as artificial enzymes that mimic cytochrome P450 enzyme (CYP450) activity. Second, artificial cells that can eavesdrop on mammalian cells in 2D and 3D are demonstrated. 

Speakers

10:15-10:30
Discussion
10:30-11:00
Coffee break
11:00-11:30
Harnessing membrane biophysical properties to investigate biological processes and design new therapeutic tools

Abstract

Membranes play a vital role in a variety of physiological processes. Recapitulating these processes outside of the cell may allow us to better understand them as well as design an entirely new class of materials that can sense, transport, or target important biological signals and molecules. In this talk, I will present our recent work using model membranes (ex. liposomes and polymersomes) and cell-free expression systems to (1) uncover the role of membrane mechanical properties on the folding of model membrane proteins and (2) design a membrane-based nanoparticle for biosensing applications. First, I will describe how membrane physical properties, such as elasticity and hydrophobic thickness, impacts the folding, location, and integration of model membrane proteins. Next, I will describe our recent work to demonstrate how compartmentalization of cell-free extracts in membranes provides new capabilities for cell-free biosensing. Our approach, bridging synthetic biology techniques and model membrane assembly, provides an innovative yet simple method to probe the role of membrane composition and biophysical properties on protein dynamics and to advance the design of drug delivery carriers. 

Speakers

11:30-11:45
Discussion
11:45-12:15
Membrane mimetic chemistry for artificial cells

Abstract

A major goal of synthetic biology is to understand the transition between non-living matter and life. The bottom-up development of an artificial cell would provide a minimal system with which to study the border between chemistry and biology. So far, a fully synthetic cell has remained elusive but chemists are progressing towards this goal by reconstructing cellular subsystems. Cell boundaries, likely in the form of lipid membranes, were necessary for the emergence of life. In addition to providing a protective barrier between cellular cargo and the external environment, lipid compartments maintain homeostasis with other subsystems to regulate cellular processes. Our lab is exploring different chemical approaches for making cell-mimetic compartments. Synthetic strategies to drive membrane formation and function, including bioorthogonal ligations, dissipative self-assembly, and reconstitution of biochemical pathways, will be discussed. Chemical strategies aim to recreate the interactions between lipid membranes, the external environment, and internal biomolecules, and will clarify our understanding of life at the interface of chemistry and biology.

Speakers

12:15-12:30
Discussion
12:30-13:30
Lunch
13:30-14:00
Synthetic Cells’ as targeted therapeutics for treating cancer and tissue engineering

Abstract

Medicine is taking its first steps towards patient-specific cancer care. Nanoparticles have many potential benefits for treating cancer, including the ability to transport complex molecular cargoes including siRNA and protein, as well as targeting to specific cell populations. 

The talk will discuss ‘barcoded nanoparticles’ that target sites of cancer where they perform a programmed therapeutic task. Specifically, liposomes that diagnose the tumour and metastasis for their sensitivity to different medications, providing patient-specific drug activity information that can be used to improve the medication choice. 

The talk will also describe how liposomes can be used for degrading the pancreatic stroma to allow subsequent drug penetration into pancreatic adenocarcinoma, and how nanoparticle’ biodistribution and anti-cancer efficacy is impacted by patient’ sex and more specifically, the menstrual cycle. 

The evolution of drug delivery systems into synthetic cells, programmed nanoparticles that have an autonomous capacity to synthesize diagnostic and therapeutic proteins inside the body, and their promise for treating cancer and immunotherapy, will be discussed.

Speakers

14:00-14:15
Discussion
14:15-14:45

Abstract

Living cells take advantage of spontaneous aggregation of certain proteins and RNA species to spatially and dynamically organize a variety of molecules and reactions. Taking inspiration from nature, our group is developing methods to build assemblies, condensates and patterns using structured motifs built with artificial DNA, that are relevant to the synthesis of self-regulated, autonomous biomaterials. I will present our recent results on controlling the rate of self-assembly and condensation and dissolution of artificial DNA motifs using chemical reactions. I will also discuss mathematical models that support and guide our experiments by capturing specific and non-specific interactions among the motifs.

Speakers

14:45-15:00
Discussion
15:00-15:30
Tea break
15:30-16:00
Matter to Life: Bottom-up assembly of synthetic cells

Abstract

The evolution of cellular compartments for spatially and temporally controlled assembly of biological processes was an essential step in developing life by evolution. Synthetic approaches to cellular-like compartments are still lacking well-controlled functionalities, as would be needed for more complex synthetic cells. With the ultimate aim to construct life-like materials such as a living cell, matter-to-life strives to reconstitute cellular phenomena in vitro – disentangled from the complex environment of a cell. In recent years, working towards this ambitious goal gave new insights into the mechanisms governing life. With the fast-growing library of functional modules assembled for synthetic cells, their classification and integration become increasingly important. We will discuss strategies to reverse-engineer and recombine functional parts for synthetic eukaryotes, mimicking the characteristics of nature’s own prototype. Particularly, we will focus on large outer compartments, complex endomembrane systems with organelles and versatile cytoskeletons as hallmarks of eukaryotic life. Moreover, we identify microfluidics and DNA nanotechnology as two highly promising technologies which can achieve the integration of these functional modules into sophisticated multifunctional synthetic cells. 

Speakers

16:00-16:15
Discussion
16:15-16:45
Establishing cell-free systems to enable a fair and sustainable 21st bio-century

Abstract

Synthetic biology (SB) is one of the most promising fields of research for the 21st century. SB offers powerful new ways to improve human health, build the global economy, manufacture sustainable materials, and address climate change. However, current access to SB-enabled breakthroughs is unequal, largely due to bottlenecks in infrastructure and education. Here, I describe our efforts to re-think the way we engineer biology using cell-free systems to address these bottlenecks. We show how the ability to readily store, distribute, and activate low-cost, freeze-dried cell-free systems by simply adding water has opened new opportunities for on-demand biomanufacturing of vaccines for global health, point-of-care diagnostics for environmental safety, and education for SB literacy and citizenship. By integrating cell-free systems with artificial intelligence (AI), we also show the ability to accelerate the production of carbon-negative platform chemicals. Looking forward, advances in engineering tools and new knowledge underpinning the fundamental science of living matter will ensure that SB helps solve humanity’s most pressing challenges.  

Speakers

16:45-17:00
Discussion
17:00-17:15
Panel discussion