Northwestern University

Teaching CRISPR in the classroom: a new tool for teachers
Photo Credit: Megan Beltran

While CRISPR has become one of the most talked about gene editing tools in the research community, easy-to-use educational activities that teach CRISPR and related molecular and synthetic biology concepts are limited. Michael Jewett and his team at Northwestern University have created a set of user-friendly educational kits to address just this issue, called BioBits kits. This tool was developed as a broader impacts activity in Dr. Jewett’s currently-funded research (NSF 1716766) , investigating and expanding the genetic code for synthetic applications such as producing non-natural polymers in biological systems, and with collaboration and funding from several other institutions.

BioBits kits contain materials to run hands-on lab activities designed to teach high school-aged students the basic concepts of synthetic and molecular biology through simple biological experiments. Students add the included DNA and water to pre-assembled individual freeze-dried cell-free (FD-CF) reactions. The results are noticeable when the individual FD-CF reactions fluoresce, release an odor, or form a hydrogel (depending on the experiment). For example, the BioBits Bright kit includes six different DNA templates, each of which encode for a protein which fluoresces a unique color under blue light, directly demonstrating how proteins differ based on initial DNA sequence. So far, three kits have been developed: BioBits Bright, Explorer, and Health, with activities covering topics from the central dogma of biology, to genetic circuits, antibiotic resistance, and CRISPR.

The visible (or smellable) outputs make the results interactive and intuitive, engaging students in a relatable experience. In addition to the FD-CF reactions and instructions, the kits contain example curriculum, such as one independent research-based activity that asks students to address ethical questions surrounding CRISPR, further engaging students in the topic and providing a deeper understanding of the technology.

Over 330 schools from around the world have requested kits so far. Find out more on the BioBits website or in recent open-access articles in Science Advances and ACS Synthetic Biology.

Sharing MCB Science: Protein synthesis by ribosomes with tethered subunits

Cells are known as the basic building blocks of life. They contain a vast number of highly specialized components to carry out the wide array of cellular functions. The ribosome is the central component responsible for protein synthesis. Previously we assumed that the ability of the two ribosomal subunits to separate from each other was required for successful protein synthesis. This assumption is now known to be inaccurate.

Dr. Michael C. Jewett, Associate Professor of Chemical and Biological Engineering at Northwestern University, and Dr. Alexander Mankin, Director of the University of Illinois Chicago’s College of Pharmacy’s Center for Biomolecular Sciences, and their colleagues have constructed a ribosome with covalently tethered subunits (dubbed “Ribo-T”). Specifically, Jewett and Mankin have engineered a ribosome where the ribosomal RNA is shared between the two subunits and linked by small RNA tethers. Dr. Mankin describes this as “two different people holding hands.” He explains, ” We have created ribosomes that can’t let go of their hands.”

This new finding leads to two different scenarios. First, these new ribosomes, or Ribo-T, are able to sustain the life of a cell without the presence of naturally occurring ribosomes. In the other scenario, Ribo-T can be used to create a ribosome mRNA system where mRNA decoding, catalysis of polypeptide synthesis and protein excretion can be optimized for new substrates and functions. This could transform the field of biomolecular engineering and synthetic biology. For example, Ribo-T can be used to explore poorly understood functions of the ribosome (e.g., antibiotic resistance mechanisms, a rising global health issue), to enable orthogonal genetic systems, or to engineer ribosomes with altered chemical properties (e.g. ribosomes that are more efficient at using non-natural amino acids). Jewett said, “a lot of people consider the ribosome to be the chef of translation and so one of the things we’re curious to know now is if you have the ability to make specialized chefs, chefs that make different types of cuisines, what kind of chefs would you make? Put another way, could we evolve the ribosome to perform new types of chemistry?” The findings of this research are described in a research article recently published in Nature.

When asked about the broader impacts of this experiment, Dr. Jewett responded:

“I view Ribo-T as a new protein-making factory, version 2.0. I think it holds promise to really expand the genetic code and our ability to produce useful molecules for society in a unique and transformative way. Our advance enables us to imagine repurposing the normal protein synthesis machinery in cells to make products that have not been possible before. This new protein synthesis is natural, but engineered. Now we open ourselves to a new world, having an expanded chemistry of living systems where we are not limited to the common building blocks.”

Dr. Jewett also added, “One of the most exciting things about this adventure is that it celebrates interdisciplinary science. The research was high-risk and a lot of people suggested that it didn’t work. Our collaborators in the Mankin lab have been phenomenal and the first authors, Erik Carlson (in my group) and Cedric Orelle were spectacularly courageous. Fortunately, we were able to use evolution in the context of engineering design to find a winner. I honestly think it is one of the reasons we were able to crack the code.”

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