Multi-scale Metabolic Modeling Research

Metabolic models of metabolism are mathematical, network-based, and large-scale representations of the set of chemical reactions for which various types of evidence exists. These models are generally reconstructed from publicly available data, or in collaboration with in vivo researchers, and their reconstruction and analysis is often accomplished using freely available programming languages and packages, or programmable computational methods. Many such models account for all reactions supported by their annotated genome, in which case they are said to be genome-scale models (GSM). GSMs span many levels of complexity ranging from purely stoichiometric to metabolic networks accounting for protein synthesis (resource analysis models) to kinetic models of metabolism. Metabolic models have been applied to a wide range of applications including bioengineering (their most typical application), investigation of metabolism, and medical applications. Examples of metabolic investigation include resolution of basic metabolic questions such as atypical energy sources, metabolic reprogramming under stress, exploring understudied pathways, multi-scale elucidation of regulation, and drug repurposing. My proposed research plan leverages the breadth of systems that can be modeled, model types, model applications, the development of new modeling techniques, and publicly available yet underleveraged datasets, along with potential collaborations within WSU and the PNNL to develop a broad program of research addressing key challenges including improved plant tolerance to heat and drought stresses, drug repurposing, and designing cyanobacteria as CO2 to biochemical platforms. These proposed applications highlight only a fraction of the breadth of modeling applications, and our lab is actively searching for collaborative in vivo and in vitro researchers with which to work to use modeling techniques to answer fundamental research questions.

Collaboration and Involvement

Seeking: Highly motivated undergraduate researchers

Multi-scale metabolic modeling is naturally collaborative and brings together a wide variety of skills and knowledges to achieve modeling goals. Because of this, student can begin contributing to this type of research early in their academic careers (as early as their sophomore year). Due to the collaborative nature of modeling research, undergraduate students need not have each skill or knowledge set, but will work together and with graduate students to make up for lack in particular areas. Undergraduate students with coursework in mathematics, computer science, and/or biology are all able to contribute, and be trained in essential skills in these other areas by graduate students supervised by the PI. Coursework at many level across multiple of the WSU curriculum will be helpful. Example helpful courses include:

  • CPT_S 111: Introduction to Computer Programming

  • CPT_S 480: Python Software Construction

  • BSCI 107: Introductory Biology: Cell Biology and Genetics

  • BSCI 201: Contemporary Biology

  • MBIOS 301: General Genetics

  • MBIOS 303: Introductory Biochemistry

  • MBIOS 478: Bioinformatics

  • Math 220: Introductory Linear Algebra

  • Math 225: Linear Algebra with Modern Applications

  • Math 364: Principles of Optimization

  • Math 464: Linear Optimization

  • Math 466: Optimization in Networks

Paid and for-credit opportunities are available, with those demonstrating financial need being more highly considered for paid opportunities. Interested undergraduate students should reach out to the PI (Wheaton Schroeder, wheaton.schroeder@wsu.edu) with your CV or resume and unofficial transcript to inquire.

Seeking: Collaborative in vivo and in vitro researchers

Metabolic models are excellent at elucidating fundamentals of metabolic systems which may be difficult or expensive to measure, as well as hypothesizing genetic interventions and experiments to improve or elucidate phenotype. As an example of what metabolic modeling can contribute to other researchers, here are some examples of research I have participated (as primary researcher or in a supervisory/mentoring role):

  • Borrowing from economics, I investigated the shadow price of protective pigment (melanin, carotenoid) production in the fungus Exophiala dermatitidis. Additionally investigated melanogenesis pathway compared to humans as a potential model system.

  • Constructed a four tissue seven stage lifecycle model of Arabidopsis thaliana for plant lifecycle modeling.

  • Investigated metabolic adaptations of Zea mays root tissue to nitrogen starvation.

  • Investigated pyrophosphate metabolism in Clostridium thermocellum to attempt to identify its primary source and

  • Construction of a three tissue diurnal model of Populus tricocarpa under control and drought conditions. Comparison of metabolism was used to hypothesize genetic interventions improving biomass yield under drought conditions.

The quality of a model is dependent on the quality of the data used in its construction. Often, the most valuable measurements for constructing models are measurements which are seen as simple, for example: growth rate and rate of uptake of the limiting nutrient. Because of this, communication with researchers before data collection can be key to quality model development.

Researchers who are interested in bringing metabolic modeling into their work are encouraged to contact the PI (Wheaton Schroeder, wheaton.schroeder@wsu.edu) to discuss potential research collaboration.