BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: gene regulation

Can CRISPR-Cas9 Cause Unwanted Change?

Dieter Egli, a biologist at Columbia University whose main goal is to better understand the differences in DNA duplication between cell types, how these differences affect genetic stability, and how certain differences affect people’s functional relevance. CRISPR-Cas9, a powerful gene-editing tool, can have serious side effects in human embryonic cells. In some cases, the consequences of these errors can be quite severe, prompting them to discard large chunks of their genetic material. 

CRISPR-Cas9 is an innovative technology that allows researchers to edit parts of genes by removing, adding, or changing sections of the DNA sequence. It is a faster, cheaper, and more accurate DNA editing technique than others such as genome editing. These techniques enable researchers to investigate the function of the gene. Researchers can use these systems to permanently modify genes in living cells and organisms, and in the future, they may be able to correct mutations at specific locations in the genetic code to treat genetic causes of disease such as blindness

DNA Repair-colourfriendly

Adapted to be accessible to those with red-green colorblindness, this image depicts DNA repair after a CRISPR-Cas9 double-strand break.

CRISPR-Cas9 embryos and other kinds of human cells have already demonstrated that editing chromosomes can cause unwanted effects. This can be in relation to the unpredictability of the repair due to the fact of different cells react differently to gene editing. Another possibility for the CRISPR-Cas9 treatment not working efficiently is a change made to sperm, eggs, or embryos that can be passed down to future generations, raising the stakes for any mistakes made along the way. An example of this would be CRISPR-Cas9 genome editing on early-stage human embryos with a mutation in the gene called eyes shut homolog, which causes hereditary blindness.

CRISPR–Cas9 efficiently edits the genome in a variety of cell types and whole organisms, repairing genetic mutations, removing pathogenic DNA sequences, and turning genes on or off in Gene Regulation, where the appropriate gene is expressed to help an organism respond to its environment.

 

 

 

Why Don´t We Grow Ears on Our Arms?

The Miracle of DNA Regulation

Now, the question posed is why we don’t grow ears on our arms. May I introduce to you: gene regulation. That’s right. Even though every single cell in your body has the same DNA, the body is able to ‘turn off’ different genes so that only ones that are necessary are read. This is why you do not grow ears on your arms, because those ear-making genes are ‘turned off’.

But… How?

This question has been plaguing scientists for quite a while, as we have discovered genes in the human genome that are ‘turned off’ but could potentially be quite useful such as the regeneration of limbs (same as a starfish or a crab). Now there has been a new breakthrough in how we understand gene regulation thanks to some researchers in Cambridge, Massachusetts. The binding domain’s function in gene regulation has been known for quite some time already. The mystery lied within the activation domain. It has now been discovered that the activation domain sort of acts as a net, capturing the molecules for gene regulation and anchoring the transcription ‘machinery’ by the gene that is to be transcribed.

But… How? What Does This Mean?

Well, the activation domain creates little droplets by mingling with transcription proteins that attract the transcription machinery stuff. It’s kind of like creating oil droplets in vinegar. This process is now called phase separation. This has grand implications for even more research on gene regulation and can even give more insight into diseases such as cancer. When do you think the next breakthrough will come? Do you think this is the key to unlocking how to turn genes on and off for good or is there much more work to be done?

 

Epigenetics and Dopamine Activity

Researchers at the University of California in Irvine have correlated erratic dopamine activity as an underlying cause of complex neuropsychiatric disorders, specifically because of the epigenetic alterations caused by low levels of dopamine. This study, overseen by Emiliana Borelli, a UCI professor of microbiology & molecular genetics, provides clues to the possible causes of complicated disorders like schizophrenia.

Dopamine is a neurotransmitter (and hormone) that fuels our daily life, acting as our prime motivator and pleasure inducer, while also being linked to memory, and cognitive function. Many addictive drugs increase the amounts of dopamine released to exhausting levels, eventually wearing out the neurotransmitters notwithstanding the negative effects of the drugs themselves. High dopamine levels can also be achieved via everyday pleasures like exercise or sex, which can also spur addiction.

Dopamine_3D_ball

Dopamine, therefore, has an irrefutable role in our everyday lives, and according to Borelli, “Genes previously linked to schizophrenia seem to be dependent on the controlled release of dopamine at specific locations in the brain. Interestingly, this study shows that altered dopamine levels can modify gene activity through epigenetic mechanisms despite the absence of genetic mutations of the DNA.”

In short, it is quite likely that Dopamine is an epigenetic hub of sorts, that can cause powerful changes in gene regulation when functioning in a disrupted or excessive manner. Borelli, knowing the consequences of excess dopamine release, tested the opposite effect on mice, hindering dopamine release by turning off mid brain dopamine receptors in rats, leading to mild dopamine synthesis. The results were profound, as Borelli found there to be decreased expression in approximately 2,000 genes in the prefrontal cortex. This epigenetic surge of decrease in genetic expression was reinforced by the increase in change of DNA proteins called histones, which are associated with reduced gene activity. The now mutated mice suffered from ranging psychotic behavior and episodes, and were then treated with dopamine activators for a duration of time before seeing their behavior normalize.

Borelli’s and others’ work will provide useful clues for understanding these complex neurological disorders, while serving to reinforce the newfound importance of comprehending gene regulation and expression. These studies seem to point to a new era in which it is not just your genetic make up that determines your future, but also the regulation of your genes.

 

 

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