Research Groups

Portrait Dora Tang

Dora Tang

Dynamic protocellular systems

Previous and Current Research

One of the grand challenges within synthetic biology is the design and construction of synthetic microsystems which mimic basic properties of natural cells. Basic biological compartmentalisation is a key property of artificial cells and existing solutions are found in self-assembled amphiphiles, polymers, inorganic molecules and protein-surfactant conjugates which form membrane delineated aqueous droplets, however the interior of these compartments are typically homogeneous and therefore do not mimic the crowded heterogeneous cytoplasm of natural cells.

This limitation can be addressed via alternative models based on liquid-liquid phase separation (coacervates) of oppositely charged macromolecules and polymers. The resulting membrane-free synthetic droplets have a chemically enriched interiors which are highly charged and crowded. As a consequence they passively sequester a range of different molecules generating a high local concentration of molecules inside the droplet1. However, low surface tension makes them relatively unstable to coalescence limiting their use in synthetic biology as discrete artificial cellular compartments2. We work across disciplines and use a variety of techniques including microfluidics, standard microscopies (electron, optical, fluorescence, confocal), spectroscopies (fluorescence, UV, CD), scattering techniques (X-ray, light), protein expression and characterization and cell-free gene expression to investigate the utility of coacervate microdroplets as robust reaction compartments and cellular mimics.

Previous work has given insights into the mechanistic pathways leading to small molecule sequestration in membrane-free coacervate protocells; successfully demonstrated the use of liquid-liquid phase separated micro compartments for protein expression using cell free expression systems; exploited microfluidics for the high throughput formation of stable, monodisperse microdroplets; and integrated two contrasting modes of protocell construction to produce a novel hybrid model based on fatty acid membrane-bound coacervate micro-droplets.

We are now focused on developing these systems further by integrating non-equilibrium processes into the design rules for the construction of activated novel protocells. To achieve this, we work between biophysics, materials science and synthetic biology to gain new insights into the physical phenomena which drive out of equilibrium processes in cells and to reimagine and translate these insights into novel, robust and dynamic systems for synthetic biology applications.

1 Koga S, Williams DS, Perriman AW, Mann S: Nature Chemistry 2011, 3:720–724
2 Williams DS, Koga S, Hak CRC, Majrekar A, Patil AJ, Perriman AW, Mann S: Soft Matter 2012, 8:6004–6014.

Dora Tang Research: Figure
Figure 1. Optical fluorescence microscopy image showing fatty acid coated coacervate microdroplets. The hybrid protocells incorporate two notions of protocell construction to generate a droplet with a highly charged crowded interior, delinaetaed my fatty acid multilayers. Increased fluorescence intensity on the outer edge shows BODIPY dye preferentially incorporated into the fatty acid multilayers. Scale bar 20 µm.
Future Projects and Goals
  1. Developing a plug and play tool kit for the construction of artificial cells, organelles and tissues with specific functions including energy conversion and metabolism.
  2. Creating a synergy between cell biology and synthetic biology to bring new insights into biological phenomena via in-vitro reconstitution.
  3. Developing new tools for simulating extreme conditions (high pressure) for cell biology and synthetic biology.
  4. High throughput synthesis of dynamic artificial systems.
Methodological and Technical Expertise
  • Protocell models
  • High pressure for soft matter
  • Cell free expression
  • Biophysical characterisation
  • Microfluidics
Selected Publications

Tang T-YD, Van Swaay D, de Mello A, Anderson JLR, Mann S
In vitro gene expression within membrane-free coacervate protocells
Chemical Communications, 51, 11429–11432

Van Swaay D , Tang T-YD , Mann S, de Mello A
Microfluidic formation of formation of Membrane-Free Aqueous Coacervate Droplets in Water
Angewandte Chemie, 2015,54, 29, 8398–8401

Li M, Huang X, Tang T-YD, Mann S
Synthetic cellularity based on non-lipid micro-compartments and protocell models
Current Opinion in Chemical Biology, 2014, 22, 1–11

Tang T-YD, Che Hak CR, Thompson AJ, Kuimova MK, Williams DS, Perriman AW, Mann S
Fatty acid membrane assembly on coacervate micro-droplets as a step towards a hybrid protocell model
Nature Chemistry, 2014, 6, 527–533

Tang T-YD, Antognozzi M, Vicary J, Perriman AW, Mann S
Small-molecule uptake in membrane-free peptide/nucleotide protocells
Soft Matter, 2013,9, 7647–7656

CV

2016
Research Group Leader, MaxSynBio, MPI-CBG, Dresden, Germany

2014–2015
Post doctoral work with BrisSynBio, University of Bristol, UK

2011–2014
Post doctoral work at Centre for Organized Matter Chemistry & Centre for Protolife Research, University of Bristol, UK

2010–2011
Knowledge Transfer Secondee, Diamond Light Source & Imperial College London, UK

2007–2010
PhD, Membrane Biophysics, Department of Chemistry, Imperial College London, UK

2007
Research Development Programme, Slade School of Fine Art, UCL, UK

2006
MSci, Department of Chemistry, Imperial College London UK

Contact

Max Planck Institute of Molecular Cell Biology and Genetics
Pfotenhauerstraße 108
01307 Dresden

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