Bio


My biggest passion is solving problems. Biotechnology is fascinating and amazingly complex; it has the power to change the world in areas such as sustainable energy, food, and medicine. Between all of these, I do not mind the exact subject so much as the process of creatively finding a solution. I look to explore and expand said creativity and problem solving skills throughout my graduate study at Stanford.

I was born in Germany and attended international schools in both Hannover, Germany, and London, England. After graduating with an IB Diploma I came to Stanford for undergraduate study in Chemical Engineering and Economics. Through an honors thesis project that covered all four years in the James R. Swartz Laboratory, I developed further depth and focus on biotechnology. I am currently enrolled as a Bioengineering student at Stanford and have worked on projects ranging from metabolic engineering of novel anti-cancer drugs to photosynthetic carbon concentration optimization to light-controlled cell division to novel HIV vaccines.

I joined the Elizabeth Sattely lab for my thesis work, and am currently engineering plant-microbe interactions. Bacteria and fungi can confer a number of beneficial properties to crops, such as improved drought tolerance and nitrogen fixation. Understanding and then engineering these mechanisms is a complex, new, and extremely hot field of research. My current project focuses on engineering the cereal-crop-symbiotic bacterium Azospirillum brasilense to excrete ammonia at high rates and over prolonged time frames. If we are successful, then this can transform sustainable agriculture for the future.

Honors & Awards


  • Accel Innovation Scholar, Stanford Technology Ventures Program (2018)
  • Bowes Fellowship, Stanford BioX (2015)
  • Firestone Honors Thesis Medal, Stanford University (2015)
  • Kennedy Thesis Prize, Stanford University (2015)
  • Mason Prize in Chemical Engineering, Stanford University (2015)
  • Terman Engineering Academic Excellence Award, Stanford University (2015)
  • President's Award for Academic Excellence, Stanford University (2012)

Stanford Advisors


Patents


  • Tim Schnabel, Elizabeth S. Sattely. "United States Patent US 62/801,454 Inducible Ammonia Excretion from a Diazotroph, Methods of Creation and Uses Thereof", Stanford University, Feb 6, 2019
  • Tim Schnabel, James R. Swartz. "United States Patent US 62/215,517 Oxygen Tolerant Iron-Iron Hydrogenases", Stanford University, Sep 15, 2015
  • Tim Schnabel. "United States Patent ND Novel DNA Aptamer Evolution", DuPont Biosciences, Aug 20, 2014

Current Research and Scholarly Interests


Engineering plant microbe interactions for improved crop properties. Focus on drought tolerance and nitrogen fixation.

Expertise: cloning, bacterial cell culture, mammalian tissue culture, plant transient gene expression, bioinformatics, GCMS/LCMS, targeted mutagenesis, random mutagenesis, protein purification, high-throughput screen development, microscopy, image analysis, microfluidic device design and fabrication, software engineering, machine learning, high-throughput data processing and visualization; proficient in R, MATLAB, Python, Java. [This is a non-exhaustive list].

Lab Affiliations


All Publications


  • Engineering post-translational regulation of glutamine synthetase for controllable ammonia production in the plant-symbiont A. brasilense. Applied and environmental microbiology Schnabel, T., Sattely, E. 2021

    Abstract

    Nitrogen requirements for modern agriculture far exceed the levels of bioavailable nitrogen in most arable soils. As a result, the addition of nitrogen fertilizer is necessary to sustain productivity and yields, especially for cereal crops, the planet's major calorie suppliers. Given the unsustainability of industrial fertilizer production and application, engineering biological nitrogen fixation directly at the roots of plants has been a grand challenge for biotechnology. Here we design and test a potentially broadly applicable metabolic engineering strategy for the overproduction of ammonia in the diazotrophic symbiont Azospirillum brasilense Our approach is based on an engineered unidirectional adenylyltransferase (uAT) that post-translationally modifies, and deactivates glutamine synthase, a key regulator of nitrogen metabolism in the cell. We show that this circuit can be controlled inducibly and we leverage the inherent self-contained nature of our post-translational approach to demonstrate that multicopy redundancy can improve strain evolutionary stability. uAT-engineered Azospirillum is capable of producing ammonia at rates of up to 500 muM h-1 OD600 -1 When grown in co-culture with the model monocot Setaria viridis, we demonstrate that these strains increases the biomass and chlorophyll content of plants up to 54% and 71% respectively relative to WT. Furthermore, we rigorously demonstrate direct transfer of atmospheric nitrogen to extracellular ammonia and then plant biomass using isotopic labeling: after 14 days of co-cultivation with engineered uAT strains, 9% of chlorophyll nitrogen in Setaria seedlings is derived from diazotrophically fixed dinitrogen, whereas no nitrogen is incorporated in plants co-cultivated with WT controls. This rational design for tunable ammonia overproduction is modular and flexible, and we envision could be deployable in a consortium of nitrogen fixing symbiotic diazotrophs for plant fertilization.Importance StatementNitrogen is the most limiting nutrient in modern agriculture. Free living diazotrophs, such as Azospirillum, are common colonizers of cereal grasses and have the ability to fix nitrogen but natively do not release excess ammonia. Here we use a rational engineering approach to generate ammonia excreting strains of Azospirillum Our design features post-translational control of highly conserved central metabolism, enabling tunability and flexibility of circuit placement. We show that our strains promote the growth and health of the model grass S. viridis and rigorously demonstrate in comparison to WT controls that our engineered strains can transfer nitrogen from 15N2 gas to plant biomass. Unlike previously reported ammonia producing mutants, our rationally designed approach easily lends itself to further engineering opportunities and has the potential to be broadly deployable.

    View details for DOI 10.1128/AEM.00582-21

    View details for PubMedID 33962983

  • Improved Stability of Engineered Ammonia Production in the Plant-Symbiont Azospirillum brasilense. ACS synthetic biology Schnabel, T., Sattely, E. 2021

    Abstract

    Bioavailable nitrogen is the limiting nutrient for most agricultural food production. Associative diazotrophs can colonize crop roots and fix their own bioavailable nitrogen from the atmosphere. Wild-type (WT) associative diazotrophs, however, do not release fixed nitrogen in culture and are not known to directly transfer fixed nitrogen resources to plants. Efforts to engineer diazotrophs for plant nitrogen provision as an alternative to chemical fertilization have yielded several strains that transiently release ammonia. However, these strains suffer from selection pressure for nonproducers, which rapidly deplete ammonia accumulating in culture, likely limiting their potential for plant growth promotion (PGP). Here we report engineered Azospirillum brasilense strains with significantly extend ammonia production lifetimes of up to 32 days in culture. Our approach relies on multicopy genetic redundancy of a unidirectional adenylyltransferase (uAT) as a posttranslational mechanism to induce ammonia release via glutamine synthetase deactivation. Testing our multicopy stable strains with the model monocot Setaria viridis in hydroponic monoassociation reveals improvement in plant growth promotion compared to single copy strains. In contrast, inoculation of Zea mays in nitrogen-poor, nonsterile soil does not lead to increased PGP relative to WT, suggesting strain health, resource competition, or colonization capacity in soil may also be limiting factors. In this context, we show that while engineered strains fix more nitrogen per cell compared to WT strains, the expression strength of multiple uAT copies needs to be carefully balanced to maximize ammonia production rates and avoid excessive fitness defects caused by excessive glutamine synthetase shutdown.

    View details for DOI 10.1021/acssynbio.1c00287

    View details for PubMedID 34591447

  • High-Throughput Screening of Catalytic H2 Production Angew Chem Int Ed Engl. Koo, J., Schnabel, T., Liong, S., Evitt, N. H., Swartz, J. R. 2017; 56 (4): 1012-1016

    View details for DOI 10.1002/anie.201610260