Blog 9: Gene Circuits

Hello again! I wanted to start this blog by mentioning that we are officially through CRISPR, for now, and can dive deeper into synthetic biology, starting today with gene circuits.

We’ve spent the last few weeks exploring how CRISPR has impacted this field. Whether it was curing diseases, growing better crops, or even fighting climate change, it seems like CRISPR has a hand in everything. But now it’s time to take things another step forward. What if, instead of just editing DNA as we’ve seen over the past few posts,there was a way to program it? Well, there is, and that’s exactly what today’s post is all about.

What are Gene Circuits?                                                                                                               

In short, Gene Circuits are a tool in Synthetic biology that gives scientists the ability to write entire paragraphs of instructions for plants and/or animals to abide by. Instead of just changing one part of DNA, scientists design entire systems of genes that control how a cell behaves. 

Here’s a visual to help you out with the rest of the explanation:

This might be a little blurry and confusing, let me break it down for you. 

Here’s a key for the image:

1) The colored arrows in the image serve as input signals. They represent signals that trigger and start the circuit. These could be anything from small molecules, to light, to the environment itself. 

2) The black line segments with half arrows represent promoters and are the starting point for the gene circuit. To reiterate, a promoter is a Biobrick that tells the cell when to start reading DNA. In the image, the different colored bars demonstrate which promoters get activated by which inputs. 

3) The rectangles that are labeled with letters like “B”, “C”, “D”, etc all represent genes or regulators. For example, module B produces a repressor or activator protein when its promoter is triggered. That protein would then go on to affect the next module, probably C or D.

** Repressors are proteins that inhibit gene expression, effectively turning "off" or reducing the production of a specific protein

**Activator proteins enhance gene expression by binding to specific DNA sequences and recruiting the cellular machinery for transcription

4. The layers are where it can get confusing for some people. In fact, it confused me the first time I looked at it. To help clarify, the layers of circuit you see are there to show the “if-then” logic that cells use. This logic can be seen for many gene circuits and works similar to any programming computer languages. Basically, scientists can edit an organism to do one thing based on the potential outcomes of another event. IF one thing is true, THEN do this…

5. Probably the easiest thing to pick up but the red arrow on the far right of the diagram represents the output of the circuit. This could be anything from proteins that emit light to chemicals that a cell should produce. 

These systems can range from simple yes-no behaviors to thousands of circuits but one thing remains the same: the logic it follows. 

Real Life Examples / Applications of Gene Circuits:

October 19th, 2017: MIT Creates Bacteria that Detects Cancer:

• Researchers at MIT’s Synthetic Biology Center, under Timothy Lu, were able to engineer E. coli with gene circuits that detected two different cancer biomarkers in the guy. If both markers are present, the trigger detects it and triggers to alert the person. 

• This creation has had a huge impact on the field of science. First, it allows for specific tumor targeting and helps mitigate the number of false positives, which is especially helpful in terms of cancer diagnosis. It also can serve as a potential lower-cost option for cancer detection moving forward. 

February 23rd, 2024: Scientists Use Gene Circuits to Make CAR-T Cell Therapy Safer

• Researchers from Stanford University and other institutions developed a gene circuit to act as a “kill switch” in CAR-T therapies. CAR-T therapy is a main cancer treatment process where doctors take a patient's T-cells(immune cells), genetically modify them to recognize and kill cancerous cells, and then put them back in the body. As good as that sounds, this type of therapy involves a lot of risks. For one, patients could develop non-related immune issues or even have off-target attacks in which the modified T-cells begin attacking the healthy cells and destroying someone from the inside out. To solve this, researchers and medical professionals used a system called inducible caspase-9 or iCasp9 to trigger modified T-cells to self-destruct if they begin causing harm. The kill switch can be activated by a simple drug and can shut down the therapy within minutes.

• This creation by scientists has had an obvious impact on the medical field by allowing patients to undergo cancer therapy without such high risks. Adding a level of control and safety to cancer therapies allows doctors to have tools that can be effective while safe for patients. 

Conclusion + WrapUp: 

After writing about CRISPR for about a month, it feels good to be back to talking about other important aspects of SynBio. 

As this field grows, gene circuits will continue to have a powerful role in programming life. From my writing today and the different examples I’ve provided, I hope you can see the important role gene circuits play in our everyday lives. 

I hope you enjoyed this week’s blog. Can’t wait to see you next time!

— Aidan Kincaid