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Synthesizing Biology Across Scales

The Center for Synthetic Biology's NRT Program

Synthesizing Biology Across Scales (SynBAS) is a National Research Traineeship (NRT) program, focused on convergent synthetic biology training for graduate students.

Through the NRT program components, students will learn the principles of living systems across scales - from molecules, to cells, to organisms, to communities.

The NRT program could offer direct financial support to graduate student trainees, as well as communications training, career mentoring, networking connections to academia and industry, and more.

Beyond the NRT programs' graduate student trainees, the courses, workshops, retreats and community events, created through this training grant, will be open to all in the synthetic biology community at Northwestern.

Click here to view the NRT program flyer!

The Scales Training Approach

Synthetic biology aims to understand and harness the rules of life across multiple scales. Life presents an enormous diversity of biological function that spans multiple spatiotemporal scales. These functions—from the abilities of cells to synthesize small molecules, remediate environmental contaminants, build and maintain ecosystems, and differentiate to protect our immune systems—have great potential to become components of sustainable solutions for meeting pressing global challenges. For example, synthetic biology research has led to engineered biological systems that can synthesize fuels, pharmaceuticals, and foods from sustainable feedstocks, act as smart therapeutics to cure diseases, and help balance the global carbon cycle. Even the seemingly simple example of cellular synthesis of products from sustainable feedstocks requires understanding and synthesis of diverse phenomena, including the underlying reaction chemical kinetics (chemistry), enzyme biophysics and substrate transport (physics), genetic regulation of enzymes and cellular physiology (biology), reactor vessel scale-up (engineering), and technoeconomic analyses (business). Synthetic biologists of the future will need training that allows them to traverse and integrate these disciplines and scales to be successful. 

At the core of our unique synthetic biology training approach is the concept of scales. Throughout its history, the field of synthetic biology has developed an inherently constructive approach, built off of the hypothesis that by understanding the rules of life we can deconstruct natural biological systems into ‘parts’ which we can re-combine to carry out customized, predictable, and useful functions. These ‘parts’ function on intrinsic length scales, combining together in a bottom-up fashion to create increasingly complex systems that have emergent behaviors across many different scales, from the molecular-level building blocks, to the cellular systems that encapsulate them, to the tissues, organisms, and communities that may eventually result, to the ethical considerations they create.

 

The Synthetic Biology Along Scales (SynBAS) training approach.

By understanding biological phenomena across multiple spatiotemporal scales - molecular, circuit/network, cell/cell-free systems, biological communities, societal - we can better construct synthetic biology solutions to address global challenges, enabling an ethically minded synthetic biology workforce.

Our training approach is to embed this concept of scales from the beginning – training students to break down synthetic biology technologies along the scales of phenomena that they require, informing how their research in a particular scale is part of a larger whole, allowing them to identify challenges that arise between scales that in turn drive further research questions. This approach allows students to think big from the beginning, incorporate societal-level considerations such as ethics into their work, and drive collaboration with other CSB labs to create impactful innovations. 

Our training program begins with coursework that teaches students how to deconstruct synthetic biology technologies along the different scales, identifying the design principles and engineering required at each scale, and the challenges between scales that must be overcome, for that application. For example, an application to develop nitrogen fixing bacteria as a more sustainable alternative to chemical fertilizers is broken down into the molecule-level nitrogenase enzymes that fix nitrogen, the network/circuit scale genetic pathways that regulate nitrogenase synthesis and assembly, the cellular scale systems that are involved nitrogen, oxygen and product transport, the cellular communities scale interactions that happen between microbes and plants in a soil ecosystem, and the societal scale questions that arise about the benefits and access to such a technology. Similar deconstructions are done for applications in biochemical production discussing the enzymes, pathways, strains and bioreactor communities needed to convert renewable feedstocks into a range of important compounds; as well as biomedical applications for example the molecular level engineering, encapsulation, delivery and immunological interactions needed to design an effective mRNA vaccine. 

Students then choose elective courses that emphasize details at particular scales related to their direct research, and courses at other scales that represent important interfaces for them to know about during their research. 

Molecular scale courses cover the physical, chemical and mathematical principles required for understanding the molecular basis of life and its use in biotechnology. These courses cover topics including the biophysics of molecular folding, free energy landscapes, kinetic molecular folding, charge screening, molecular interactions, RNA folding, protein folding, enzymology and others. These courses also use these principles to teach concepts related to RNA and protein design and experimental strategies for RNA and protein engineering. 

Network/circuit scale courses enable students to understand biological, mathematical and biophysical principles underpinning the mechanisms that biological systems utilize to propagate information, coordinate physiological states, and implement control over those states.  These courses cover topics such as genetic circuits, metabolism, dynamical systems, network theory and mechanisms for intracellular and intercellular signaling and communication. 

Cell/cell-free systems scale courses cover biophysical and chemical principles involved in engineering biological parts within living and cell-free systems. These courses can include topics such as cellular and cell-free enzymatic biosynthesis, the implementation of genetic circuits in cell and cell-free systems, transport phenomenon at the cellular scale, interactions between cells/tissues and biomaterials, techniques for the manipulation of systems at this scale, and the use of cell-free systems as platforms for discovery and diagnostics.  

Biological communities scale courses cover the biological, biochemical and mathematical principles required for understanding the emergent behavior of cellular communities. These courses include topics such as microbial ecology and metagenomics, prediction of emergent microbial community dynamics, interspecies metabolic interaction, tissue-scale phenomena such as tissue engineering, microbial ecology, and modeling of biological communities including agent-based models and nonlinear differential equation models. 

Societal scale courses address topics such as bioethics related to synthetic biology. The also teach students the skills needed to quantitatively estimate the needs, market sizes and viability of synthetic biology technologies including frameworks of field trials, user testing, and stakeholder analysis.

This coursework is a launch pad towards impactful research in the training program that allows students to use the scales framework to identify the most important scale to the success of a particular application and key engineering opportunities and challenges between scales for ultimate impact. Ethical considerations which underlie every research decision we make will be integrated in training across coursework, workshops, experiential projects, and research projects. By identifying a co-mentor with expertise at a different scale than their primary research mentor, trainees can further explore concepts introduced through the scales framework in their own research and develop exciting collaboration opportunities. 

In this way the scales framework is the focal point of the SynBAS NRT program, and drives the training and research across the Northwestern Center for Synthetic Biology. 

Program Components

The SynBAS NRT training program consists of several key components and activities that students pursue throughout their time in the CSB.

 

2021-2022 Application Cycle

The 2021-2022 NRT is now live. To submit the application and for application instructions, please see our Application Page.

 

Application Requirements:

Application Timeline:

NRT Program Leadership

NRT Faculty Members

Program Coordinator

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