Editing the Building Blocks of Life, Using a New Technique

Undergraduates at Humboldt State can edit genomes using CRISPR, a technology introduced on campus last year.
In a bustling laboratory, Biology 410 students are clustered into groups of two or three, pipetting fluids into tiny test tubes. The scene isn’t unusual for an upper level course in a science classroom, but these students are doing something previously unseen in undergraduate courses: editing genomes.
Image

Using the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated gene 9)-based techniques, students in Biology Professor John Steele’s classes and labs have been editing the genetic material of cells, inserting coding sequences for fluorescent proteins, correcting or inserting disease-causing mutations, or mutations that affect other cell functions, or studying pathways using CRISPR-based modifiers of gene expression.

Dr. Steele received his Ph.D. and did his post-doctoral work in neurodegeneration labs, looking at a spectrum of diseases such as Alzheimer’s, Huntington’s, and Parkinson’s, as well as several rare neurological diseases. The cell death involved in those diseases is caused by a buildup of proteins—an apparent inability to activate the autophagy pathway, or the cells’ way of maintaining themselves.

In his BIOL 410 class this semester, students are using CRISPR-based methods to control expression of genes in human embryonic kidney cells, then studying how the loss or overabundance of the genes effect the autophagy pathway—leading to more understanding about what causes neurodegenerative diseases.

Dr. Steele brought these CRISPR techniques to HSU when he was hired in Fall 2016. Until several years ago, before the technique was developed, genome editing would have cost tens of thousands of dollars and taken six weeks or more. Now, with CRISPR-based methods, genome-editing tools can be easily produced by students in his lab courses for around $20 and completed in a week.

Because of the low cost and relative simplicity of the CRISPR techniques, Dr. Steele has given it classroom applications new to undergraduate programs.

The way CRISPR edits genomes is closely related to fundamental biology teachings. Students in entry-level courses are learning the principles that make CRISPR function, and then will be able to apply those principles in a hands-on way in later courses. And he’d like to introduce CRISPR even earlier in biology students’ educations.

“From a pedagogical standpoint, it’s a really effective way to teach the central dogma of genetics,” Steele says. “CRISPR will be the foundational research tool of the gene editing field and students need to learn how to work with these tools now.”

Image

It’s also a highly marketable skill. Recent graduates have already landed jobs in academic and private laboratories based partly upon their experience with CRISPR-based methods.

As part of his curriculum, Steele asks students to propose research ideas using the highly adaptable CRISPR process.

Patrick Quinn, a Psychology graduate student, is seeking to use CRISPR to manipulate expression of multiple genes at a time, improving his understanding of schizophrenia and other neurodevelopmental disorders.

Biochemistry Senior Michael Martinez, who says he “pretty much kicked down John’s office door and said let me work here” when he learned of Dr. Steele’s CRISPR lab, is researching the how overabundance of the protein tau alters cellular processes in human embryonic kidney cells, similar to Steele’s work. Interested in the building blocks of life, Martinez originally wanted to design tools like CRISPR—now he can use it to conduct research at a scale previously unattainable.