Martin Fussenegger's Biotechnology and Bioengineering Research Group

Synthetic Biology: From Biotechnology to Human Therapy

Human diseases originate from spontaneous, environmentally-triggered or pathogen-induced perturbations of endogenous expression or signaling networks, and often result in disabling or fatal pathologies. Beyond administration of small-molecule drugs or biopharmaceuticals, currently available treatment concepts include reprogramming of genetic deficiencies using gene-transfer technologies, and implantation of engineered cells or tissues. Focusing on engineering of mammalian cells using synthetic biology principles we are designing the treatment strategies of the future.

Synthetic Receptors for Programmable i/o Relationships

We are creating synthetic receptors with adaptable ligand-binding domains to sense relevant soluble or surface-bound antigens. This can be combined with appropriate response modules to control expression of endogenous or exogenous genes.

Selected publications:
Scheller et al., 2018, external pageNat. Chem. Biol. 14: 723
Kojima et al., 2018, external pageNat. Chem. Biol. 14: 42

In the press:

external pageThe Scientist

Immuno-mimmetic Cells

We are genetically engineering easy-to-use non-immune cells with synthetic gene circuits so that they can mimic and boost immune cell function in the treatment of infection or cancer.

Selected publications:

Liu et al., 2018, external pageCell 174: 259
Kojima et al., 2018, external pageNat. Chem. Biol. 14: 42

In the press:
external pageNeue Zürcher Zeitung, 20 Minuten, external pageThe Scientist
 

Synthetic Gene Switches

We keep increasing the collection of novel trigger-inducible transgene expression systems for precise dosing of in-situ production of protein therapeutics.

Selected publications:

Wang et al., 2018, external pageNat. Biomed. Eng. 2: 114
Bojar et al., 2018, external pageNat. Commun. 9: 2318
Liu et al., 2018, external pageNuclei Acid Res, gky805

In the press:
external pageNat. Biomed. Eng. News and Views, external pageThe Guardian, external pageThe Scientist, external pageDaily Mail

Programmable Biocomputers

We have been designing input-programmable genetic devices with digital expression logic that may interface and communicate with electronic devices.

Selected publications:
Auslander et al., 2018, external pageNat. Methods 15: 57
Muller et al., 2017, external pageNat. Chem. Biol. 13: 309
Auslander et al., 2014, external pageNat. Methods 11: 1154

In the press:
external pageNature Chemical Biology News and Views, external pageNature Methods  

Prosthetic Gene Networks

We have been assembling closed-loop metabolic control circuits that sense disease metabolites and coordinate therapeutic protein production in a seamless and automatic manner.

Selected publications:
Ye et al, 2017, external pageNat. Biomed. Eng. 1: 5
Chassin et al., 2017, external pageNat. Commun. 8: 1101
Xie et al., 2016, external pageScience 354: 1296

In the press:
external pageNat. Biomed. Eng. News and Views, external pageNat. Rev. Mol. Cell Biol. - Research Highlight
 

Cell-based Diagnostics

One of our aims has been to engineer cells with gene circuits to sense disease-relevant markers and respond by producing easily measurable outputs. These cells can be applied in diagnosis, either ex vivo, by exposing cells to human clinical samples, or in vivo, by implanting them in the body.

Selected publications:
Tastanova et al., 2018, external pageScience Transl Medicine 10(437): eaap8562
Auslander et al., 2014, external pageNat. Commun. 5: 4408

In the press:
USA Today, external pageBBC News, external pageMedical News Today, external pageThe Telegraph

Synthetic Lineage Control

We have been designing synthetic cell-fate control gene circuits for rational programming of stem cell differentiation, as well as transdifferentiation of multipotent cells to achieve therapeutically relevant cell phenotypes for cell-based therapies.

Selected publications:

Saxena et al., 2016, external pageNat. Commun. 7: 11247
Schukur et al., 2015, external pageScience Transl Medicine 7: 318

In the press:
external pageLiveScience, external pageThe Telegraph, external pageNature, external pageScience, external pageBioworld (Thompson Reuters), external pageThe Scientist
 

Drug Discovery

In collaboration with biotech companies, we have been working on the discovery of novel cytostatic, immunosuppressive and anti-infective drugs using engineered mammalian sensor proteins and tissue culture systems.

Selected publications:
Sedlmayer et al., 2018, external pageNat. Commun. 9: 1822
Weber et al., 2008, external pagePNAS 105: 9994

In the press:
external pageCell
 

Non-Neural Optogenetics

We have been developing synthetic photo-transduction cascades in mammalian cells such that light-controlled transgene expression can be used to program cellular and tissue behaviour.

Selected publications:
Kim et al., 2015, external pageAngew. Chem 54: 5933
Folcher et al., 2014, external pageNat. Commun. 5: 5392
Ye et al., 2011, external pageScience 332: 1565

In the press:
external pageThe Guardian, external pageNature Reviews Urology, external pageWallstreet Daily, external pageNature, external pageThe Telegraph, external pageMIT Technology Review, external pageCell, external pageNature Medicine, external pageScience Signaling
 

Synthetic Gene Networks

Design of complex synthetic gene networks to program dynamic control of key metabolic networks in mammalian cells and tissues.

Selected publications:
Bacchus et al., 2012, external pageNat. Biotechnol 30: 991
Tigges et al., 2009, external pageNature 457: 309

In the press:
external pageNature News, external pageTechnology Review Published by MIT
 

Biopharmaceutical Manufacturing

Design of prototypic biopharmaceutical manufacturing strategies by integrating engineering of mammalian production cell lines for increased secretion of high-quality biologics with upstream process development.

Selected publications:
Auslander et al., 2014, external pageMolecular Cell 55: 397
Fussenegger et al., 1998, external pageNat. Biotechnol. 16: 468
 

Funding
ERC Advanced grants (ElectroGene 2018; ProNet 2012), CTI/Innosuisse.

Enlarged view: Synthetic biology: mapping the scientific landscape
Oldham et al. 2012. Synthetic biology: mapping the scientific landscape. PLoS One, 7(4) e34368

Contact
If you want to join our lab for your Master Thesis, please send your application to (motivation letter, CV, and your transcripts).

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