Have you ever watched an audience of star-struck biologists? It’s much like attending a pop concert. The age distribution is skewed slightly older, but much like attendees at a concert they already know most of what the speaker is going to say (and could probably even sing the words!) but they attend anyway to nod along happily with the celebrity.

If that sounds like your jam, or you want to learn about the current state of genetic engineering, you’ll get your chance this Sunday. On January 28th, Dr. Feng Zhang—biochemist at MIT, Harvard, and the McGovern Institute for Brain Research—is giving a public seminar at CU Boulder. Zhang is a pioneer in the field of genetic engineering, especially when it comes to a set of tools called CRISPR-Cas systems.

feng zhang

When scientists mess around with the DNA of an organism to change one or more of its features, we call it genetic engineering. These days scientists can take a lab plant, animal, or other creature—anything from a humble bacterium to a mouse—and alter the genetic code of its progeny, or descendants. For example, scientists have genetically engineered mice to glow bright green under ultraviolet light. When studying how genes work and how they can occasionally go wrong, the ability to intentionally change genes is a very useful tool for scientists to have at their disposal.

Sometimes genetic engineering is done at random—scientists create single mutations (changes in the DNA) at different points in a gene and observe the outcome. For example, in the past scientists made random mutations in crops and observed which of these mutations made larger, tastier ears of corn.

But genetic engineering can also be exquisitely directed and specific. If you know the sequence of a gene, relatively new biotechnology means that you can redesign the gene exactly the way you want it. In the past, methods to make specific desired changes in genes, especially genes in human DNA, were very difficult to use and not very efficient. Scientists had to spend a lot of time hunched over petri dishes before they got the exact mutation they wanted.

Zhang, along with other incredible scientists such as Dr. Jennifer Doudna at UC Berkeley, was part of a revolution in genetic engineering. He found that an element of the bacterial “immune system” could be harnessed to engineer animal genes.

Wait—bacteria have immune systems? Well, sort of. They don’t sneeze or get fevers, but they can be infected by viruses. Viruses that infect bacteria are called “phage,” and they can be very deadly if you’re a poor little Escherichia coli. But just like humans have evolved an immune system to help us fight off the flu, bacteria have evolved a nifty way to fight off their bugs.

When a phage infects a bacterial cell, it will sometimes kill the bacterium. But other times, the bacterium wins and the phage is inactivated instead. In that case, the bacterium will scoop up some of the phage DNA and stick it in its own genome. This might seem like an odd thing to do, but it’s actually incredibly beneficial if another, identical phage ever stages another attack. The bacterium can refer back to its own DNA, and use this “prior knowledge” of infection to defeat the second infecting phage. It’s like the bacterium carries around a vaccination card (a term coined in Doudna’s lab) at all times, with information about what has infected it in the past.

Every time a bacterium puts a piece of phage DNA into its own genome, it puts it next to all the other pieces it has there already. Each piece of phage DNA is separated by some spacer DNA, and this highly repetitive region is called Clustered Regularly Interspaced Short Palindromic Repeats, or CRISPR.

CRISPRfigure-01

There are also some genes close to the CRISPR region called Cas genes, or CRISPR-associated system genes. These code for important proteins that allow bacteria to use the embedded phage DNA. The bacteria use phage DNA to create RNA, which is similar to DNA but only has one strand where DNA has two strands. The Cas proteins grab onto this RNA and use it to hunt down the phage genome to destroy it.

Biochemists realized they could exploit this neat trick for their own devices. By taking the Cas proteins, but giving it RNA from a human gene, they made the Cas protein target human DNA for destruction. Thus, the CRISPR-Cas system can efficiently get rid of any gene that scientists want to target! In recent years, this has been fine-tuned and adapted so that the Cas protein doesn’t have to get rid of the DNA; it can replace the DNA with a different sequence instead. This means that the CRISPR-Cas system can be used to specifically alter DNA exactly the way that scientists want it to be altered. (For a more detailed description of how CRISPR works, see this recent Vox article.)

Biologists went bananas over how easy the CRISPR-Cas system is to use in almost any lab animal. In fact, using CRISPR-Cas to edit genes is so easy and efficient that it’s already being seriously talked about for gene therapy. Companies in the United States (including Zhang’s company) have started investigating the possibility of using it to treat disease. Recent reports from clinical trials in China suggest that it can treat cancers in humans. Whether these early trials are safe and effective remains to be seen, but there’s no doubt that CRISPR has already revolutionized genetic engineering and biotechnology-based medical intervention.

At Sunday’s seminar, hosted by the Keystone Symposia Community Lecture Series, Zhang will speak about this revolution and discuss the implications to the world at large. Whether you’re there to learn about the significance and repercussions of modern genetic engineering, or to enjoy how dazzled your local biologists are by a pioneer in their field, it promises to be an illuminating talk. For more, see the event page.

By Alison Gilchrist (@AlisonAbridged)

Posted by Science Buffs

A CU Boulder STEM Blog

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