Tillman U. Gerngross

Research Interests

Protein engineering; glycoprotein engineering; high cell density fermentation technology; metabolic engineering; protein expression

Education

• BS/MS, Chemical Engineering, Technical University of Vienna, Austria 1989
• PhD, Molecular Biology, Technical University of Vienna, Austria 1991

Awards

• National Academy of Engineering (NAE) Member, 2017

Startups

Research Projects

• Glyco-engineering of proteins

  Glyco-engineering of proteins

  Glyco-engineering of proteins is being developed as a method to control the composition of glycans on glycoproteins. Such methods are of great importance in the biopharmaceutical industry because glyocoproteins constitute over 60% of all approved therapeutic proteins; and the therapeutic properties of many glycoproteins strongly depend on the composition of their glycans.

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• Humanization of glycosylation in yeast

  Humanization of glycosylation in yeast

  Humanization of glycosylation in yeast enables the use of yeast-based protein expression systems which offer inherent advantages over conventional mammalian cell culture. By engineering yeast-based systems to perform human-like glycosylation fully-humanized therapeutic proteins can be produced in these glyco-engineered hosts.

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• Novel protein expression systems

  Novel protein expression systems

  Novel protein expression systems are being developed based on the soil bacterium Ralstonia eutropha as an alternative to E.coli-based protein expression. This bacterial host can be grown to cell densities in excess of 150g/l in ultra high cell density culture and allow for the recovery of proteins that are prone to inclusion body formation in E.coli. Specific model proteins have been expressed at levels 100 fold higher than in E.coli thereby providing the impetus for further developing Ralstonia eutropha for the production of therapeutic proteins including monoclonal antibodies and peptides.

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• Cellular engineering of protein expression hosts

  Cellular engineering of protein expression hosts

  Cellular engineering of protein expression hosts provides the ability to modify proteins in a site specific and controlled fashion—something increasingly important for the development of therapeutic proteins. We are developing methods by which cells are genetically engineered to incorporate sugars on a recombinant protein in a site-specific sequence dependent manner. Once a sugar is positioned on a given protein, conventional chemical modification such as PEGlylation can be used to further modify the protein and improve its therapeutic properties.

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• Cell-based protein purification systems

  Cell-based protein purification systems

  Cell-based protein purification systems offer advantages over conventional protein purification approaches which rely mostly on chromatographic methods to stepwise enrich for a desired protein of interest. We are developing approaches by which cells are engineered to produce their own affinity matrix to selectively sequester a desired recombinant protein. This allows for the expression and affinity purification of desired proteins in a single host, thereby obviating the need for external chromatographic purification.

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• Fermentation processes

  Fermentation processes

  Fermentation processes with high cell densities are important for the production of most bio-therapeutics which is conducted in highly controlled fed-batch processes. Commercial yeast- and E.coli-based fermentation processes often reach cell-densities in excess of 50g/l in fed-batch culture. Our laboratory has developed processes for the high cell density cultivation of Ralstonia eutropha allowing us to reach cell densities of over 150g/l and the expression of recombinant proteins at titers exceeding 10g/l. Much of this is achieved by implementing computer controlled feeding algorithms.

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Selected Publications

• Gerngross, T.U. It's the problem, stupid! Nature Biotechnology, 30, 742–744 (2012) (Full Text Version)
• Hamilton, S.R., R.C. Davidson, N. Sethuraman, J.H. Nett, Y. Jiang, S. Rios, P. Bobrowicz, T.A. Stadheim, H. Li, B-K. Choi, D. Hopkins, H. Wischnewski, J. Roser, T. Mitchell, R.R. Strawbridge, J. Hoopes, S. Wildt, T.U. Gerngross. Humanization of Yeast to Produce Complex Terminally Sialylated Glycoproteins. Science, 313(5792):1441-1443 (2006) (Abstract, Full Text Version)
• Li, H., N. Sethuraman, T.A. Stadheim, D. Zha, B. Prinz, N. Ballew, P. Bobrowicz, B-K. Choi, W.J. Cook, M. Cukan, N.R. Houston-Cummings, R. Davidson, B. Gong, S.R. Hamilton, J.P. Hoopes, Y. Jiang, N. Kim, R. Mansfield, J.H. Nett, S. Rios, R.l. Strawbridge, S. Wildt, T.U. Gerngross. Optimization of humanized IgGs in glycoengineered Pichia pastoris. Nature Biotechnology. 24, 210 - 215 (2006)
• Hamilton, S.R., H. Li, H. Wischnewski, A. Prasad, J.S. Kerley-Hamilton, T. Mitchell, A.J. Walling, R.C. Davidson, S. Wildt, and T.U. Gerngross. Intact {alpha}-1,2-endomannosidase is a typical type II membrane protein. Glycobiology. 15(6):615-24 (2005)
• Wildt, S., and T.U. Gerngross. The humanization of N-glycosylation pathways in yeast. Nature Reviews Microbiol. 3(2):119-28 (2005)
• Gerngross, T.U., Advances in the production of human therapeutic proteins in yeasts and filamentous fungi. Nature-Biotechnology, 1409 -1414 (2004)
• Hamilton, S.R., P. Bobrowicz, B. Bobrowicz, H. Li, T. Mitchell, J.H. Nett, S. Rausch, T.A. Stadheim, S. Wildt, H. Wischnewski, and T.U. Gerngross. Production of complex human glycoproteins in yeast. Science, 301, 1244 (2003) (Abstract, Full Text Version)

News

Inauguration Panel Highlights Innovation
Sep 22, 2023

Faculty and Staff Named to Top NH Business Leaders List
Jan 03, 2022

The Battle Against COVID-19
Apr 08, 2021

Innovation Prizes Presented at Virtual Entrepreneurs Forum
Oct 16, 2020

Gerngross Starts Antibody Company to Fight Coronaviruses
Aug 06, 2020

Dartmouth Professor Gerngross Elected to National Academy of Engineering
Feb 09, 2017

Dartmouth's Gerngross and Davis Set Sights on New Challenges
Jun 14, 2016

Dartmouth funded as an NSF Innovation Corps Site
Apr 15, 2016

Dartmouth Names New Director of Technology Transfer
Jul 15, 2015

Trustees Discuss Academic Vision, Resources, and Planning
Sep 16, 2014

Tillman Gerngross: On Biotech and the Entrepreneurial Spirit
Jun 23, 2014

NAE Presents Nation's Top Prize for Engineering Education to Dartmouth
May 14, 2014

Dartmouth Engineering Professor Named a 2013 National Academy of Inventors Fellow
Dec 10, 2013

President Hanlon Announces Founding of Student Innovation Center
Sep 25, 2013

Should we be making plastic from plants?
Sep 18, 2013

Two to Lead Office of Entrepreneurship & Technology Transfer
Apr 11, 2013

Dartmouth Bioengineers Develop Humanized Yeast
Mar 06, 2011

Dartmouth researchers put recycling in perspective
Mar 06, 2011

Engineering profs chosen as NH "Entrepreneurs of the Year"
Mar 06, 2011

Dartmouth and GlycoFi Report Full Humanization of Therapeutic Proteins from Yeast
Mar 06, 2011

Dartmouth engineers closer to mass-producing therapeutic proteins
Mar 06, 2011

NCI Awards $12.8 Million to Dartmouth Center of Cancer Nanotechnology Excellence
Mar 06, 2011

Merck & Co., Inc. to Acquire GlycoFi, Inc.
Mar 06, 2011

Dartmouth Engineering Professors Secure $7 Million
Mar 04, 2011

In the News