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: 723call_made
Kojima et al., 2018, external pageNat. Chem. Biol. 14: 42call_made
In the press:
external pageThe Scientistcall_made
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: 259call_made
Kojima et al., 2018, external pageNat. Chem. Biol. 14: 42call_made
In the press:
external pageNeue Zürcher Zeitungcall_made, 20 Minuten, external pageThe Scientistcall_made
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: 114call_made
Bojar et al., 2018, external pageNat. Commun. 9: 2318call_made
Liu et al., 2018, external pageNuclei Acid Res, gky805call_made
In the press:
external pageNat. Biomed. Eng. News and Viewscall_made, external pageThe Guardiancall_made, external pageThe Scientistcall_made, external pageDaily Mailcall_made
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: 57call_made
Muller et al., 2017, external pageNat. Chem. Biol. 13: 309call_made
Auslander et al., 2014, external pageNat. Methods 11: 1154call_made
In the press:
external pageNature Chemical Biology News and Viewscall_made, external pageNature Methodscall_made
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: 5call_made
Chassin et al., 2017, external pageNat. Commun. 8: 1101call_made
Xie et al., 2016, external pageScience 354: 1296call_made
In the press:
external pageNat. Biomed. Eng. News and Viewscall_made, external pageNat. Rev. Mol. Cell Biol. - Research Highlightcall_made
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): eaap8562call_made
Auslander et al., 2014, external pageNat. Commun. 5: 4408call_made
In the press:
USA Today, external pageBBC Newscall_made, external pageMedical News Todaycall_made, external pageThe Telegraphcall_made
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: 11247call_made
Schukur et al., 2015, external pageScience Transl Medicine 7: 318call_made
In the press:
external pageLiveSciencecall_made, external pageThe Telegraphcall_made, external pageNaturecall_made, external pageSciencecall_made, external pageBioworld (Thompson Reuters)call_made, external pageThe Scientistcall_made
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: 1822call_made
Weber et al., 2008, external pagePNAS 105: 9994call_made
In the press:
external pageCellcall_made
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: 5933call_made
Folcher et al., 2014, external pageNat. Commun. 5: 5392call_made
Ye et al., 2011, external pageScience 332: 1565call_made
In the press:
external pageThe Guardiancall_made, external pageNature Reviews Urologycall_made, external pageWallstreet Dailycall_made, external pageNaturecall_made, external pageThe Telegraphcall_made, external pageMIT Technology Reviewcall_made, external pageCellcall_made, external pageNature Medicinecall_made, external pageScience Signalingcall_made
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: 991call_made
Tigges et al., 2009, external pageNature 457: 309call_made
In the press:
external pageNature Newscall_made, external pageTechnology Review Published by MITcall_made
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: 397call_made
Fussenegger et al., 1998, external pageNat. Biotechnol. 16: 468call_made