BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: cell cycle

Cell Cycle Regulation in Revolutionary Gene Editing Technique (a.k.a. CRISPR)

There are more than 500 different types of human cancers. Wouldn’t it be wonderful if scientists could develop cures for all of them? Scientists believe that CRISPR gene-editing can be used to cure some cancers. CRISPR (an acronym for clustered regularly interspaced short palindromic repeats) is a way of targeting a specific bit of DNA inside a cell which can then be gene-edited to change such bit of DNA. CRISPR has also been used for other purposes, such as turning genes on or off without changing their DNA sequence.

 

Recent research has found a link between CRISPR gene-editing and mutated cancer cells. Scientists believe that a further understanding of this link can identify a group of genes which should be monitored for mutations when cells are subjected to the CRISPR gene-editing method. Although CRISPR gene-editing holds promise for cell repair, the application of CRISPR gene-editing, which is meant to identify and correct damage in cells, can also cause damage to cells in a controlled manner. Such damage activates a protein, p53 (“also known as the guardian of the genome”), which helps repair damaged DNA. 

CRISPR-Cas9 mode of action

P53 is a transcription factor, which is a protein that regulates the rate at which DNA is transcribed into RNA. These transcription factors bind to regulatory sequences in proteins, thus changing the shape of DNA, ultimately making them the most vital form of gene regulation. Transcription factors include many proteins but exclude RNA polymerase, which pries two strands of DNA apart and joins two strands of DNA together (Campbell, 280). P53 works by sliding along the damaged DNA, seeking a critical site to which it attaches and then sends a message to halt cell division until the DNA is repaired. In other words, p53 acts as a checkpoint in the cell cycle, preventing cell from proceeding though the G1 and G2 phases of the cell division cycle. In mice, the same exact transcription factor exists; those that lacked the Trp53 gene developed tumors at a far faster rate than those with the functioning gene.

 

By using CRISPR technology to damage DNA at the same cite at which DNA damage occurs, scientists are able to identify the protein responsible for cellular proliferation. If damage to the cell is too severe then p53 triggers apoptosis (the death of cells which occurs as a normal and controlled part of an organism’s growth or development) so that the damaged cell is destroyed. However, sometimes p53 is itself damaged which prevents such protein from binding to the damaged DNA in order to repair it or otherwise signaling destruction of the cell. When this occurs, the damaged cells multiply and grow, resulting in tumors. Scientists have found alterations in p53 in more than half of all cancers and thus, consider p53 the most common event in developing cancer.

 

New studies show that p53 inhibition can make CRISPR more effective thus, counteracting “enrichment” (the process of purifying cells for downstream applications such as qRT-PCR, cell polarizations ex vivo, or to enrich cells for use in a flow cytometry experiment) of cells with p53 mutations which has been observed to occur in cell cultures when such cells have been subjected to CRISPR. In other words, there is in vitro evidence that CRISPR technology causes harmful p53 mutations to be more prevalent in the population that has been subjected to the CRISPR technique. These findings suggest that there is a group of genes that should be monitored for mutations when the CRISPR gene-editing method is applied to cells. 

 

Cancer is a devastating disease that has taken the lives of many people. Members of my family have suffered and lost their battle to cancer (most recently my dear aunt this past weekend). CRISPR presents the possibility of finding cures to cancer which are specifically designed to target the particular genetic mutations that are unique to each individual. Perhaps, the cure to cancer will be achieved sooner than we realize,  although clearly not soon enough. 

 

Works Cited:

Reece, Jane B, and Neil A. Campbell. Campbell Biology. Boston: Benjamin Cummings / Pearson, 2011. Print.

Cellular GPS: A New Cancer Treatment

In recent years, it is estimated that 40% of people will face cancer during their lifetime. Still, there exist few reliable treatments for cancer, whereby it has become one of the leading causes of death in the world. Ideally, if a tumor is confined to one area of the body and is easily accessible, doctors may simply try to remove it with surgery. However, tumors are usually widespread and not so easily identifiable, whereby doctors turn to treatments such as chemotherapy which causes mass death of both healthy and unhealthy cells throughout the body. Nonetheless, scientists have discovered a potentially more targeted treatment for cancer, involving guiding magnetic seeds to tumors and burning them.

Bodily cells undergo the cell cycle, a controlled series of stages referred to as interphase, mitosis, and cytokinesis. Interphase is comprised of the G1, S, and G2 phases where cells perform normal activities, grow, undergo DNA replication, and duplicate organelles. Next, mitosis marks the division of the nucleus while cytokinesis marks the division of the cytoplasm. During this process, there are “checkpoints” at the end of the G1 phase, G2 phase, and mitosis. For example, maturation-promoting factors may trigger a cell’s passage through the G2 checkpoint if it has successfully duplicated and grown or stop a cell’s passage through this gateway if it has incorrectly copied itself. Cancer is caused when mutations in certain genes cause uncontrollable cell growth; this unchecked and rapid division causes many cells to pack closely together into tumors which hijack bodily functions, ultimately proving fatal unless treated.

Recently, researchers have proposed a new method to treat cancer patients, especially those with tumors in hard-to-reach places like the cranium. This treatment would send a highly magnetic thermoseed into one’s body which would be remotely heated once at the site of the tumor. Here, like driving a car on a loopy road, a doctor would use an MRI scanner to carefully guide the magnetic seed through the patient’s body. MRI scanners are reliable tools in scanning the location of tumors, so they would accurately pinpoint where to target and where to avoid with the thermoseed. Thus, this controlled method of eradicating tumors poses less of a threat with regard to damaging the body as a whole or even damaging surrounding tissues.

Although the prospect of such innovative research for remedies fuels optimism, it surely raises the question of which patients should undergo the new thermoseed treatment rather than well-trusted treatments like chemotherapy or open surgery. According to the study, this method would be greatly influential in treating glioblastoma, a common brain cancer. With traditional open brain surgeries, patients merely survive a year to a year and a half on average. Moreover, side effects are always a large risk with many current cancer treatments. However, I believe that killing the tumor remotely with a thermoseed and MRI has the potential to be a breakthrough, successfully eliminating the tumor and posing fewer long-lasting effects. While this treatment is still an idea at the beginning stages of research, its projected benefits make me optimistic about its future.

What do you think? Will this proposed cancer treatment be the reliable cure scientists have been looking for or a futile treatment that only reminds us of the challenge we are up against?

New research exposes and demonstrates how damaged cells survive the cell cycle

In recent news, the Center for Cancer Research have recently discovered a previously unknown phenomenon, which allows certain cells to continue through the cell cycle despite experiencing DNA damage. This also includes past natural safety checkpoints within the cell cycle that are designed to stop the problem from occurring. On January 13, 2021 researchers, in Science Advances, suggested that the timing of DNA damage was crucial for determining whether a faulty cell would survive the cycle.

When cells begin to divide and replicate as part of their natural cycle, they transition from their resting state to one called the G1 phase. In this phase, cells have several important checkpoint mechanisms to ensure that the cell is healthy enough to proceed onto the next stage of the cell cycle. If/when these mechanisms fail due to genetic mutations, cells can progress through the G1 phase unobstructed, which can ultimately lead to cancer.

It was previously believed that cells with DNA damage could not pass through these safety checkpoints in the G1 phase and that the cells would either repair the DNA damage or die. However, scientists helped uncover evidence proving that cells with damaged DNA can actually progress past these critical checkpoints. A team of scientists studied individual cells for days at a time, using live cell time-lapse microscopy, single-cell tracking software, and fluorescent biosensors to detect the cell’s safety checkpoint mechanisms. They added a substance to induce DNA damage for cells of different ages in the cell cycle. Strikingly, the majority of cells seemed to ignore the DNA damage because they failed to trigger the checkpoint between G1 and the next phase, and proceeded into the next phase anyway.

Further investigation revealed that the timing of DNA damage during the cell cycle influenced the likelihood that damaged cells would slip past the checkpoints. The researchers found that the cell’s response to DNA damage is relatively slow compared to the speed of the cell cycle. This means if cells were already very close to the next phase of the cell cycle at the time DNA damage happened, they were more likely to continue into that phase. If the cells were still early in the G1 phase, they were more likely to revert back to a resting state. These observations are a form of inertia, where the cell will continue moving towards the next phase regardless of safety checkpoint signals.

It was also discovered that cells which were genetically identical were more likely to share the same cell cycle fate than non-identical cells. This suggests that factors specific to the cells themselves influence their fate during the cycle, rather than random chance. More studies are needed to understand how these findings apply to cancer. Testing is also extremely important in order to fully understand what the long-term consequences of the checkpoint failures are and find out if the cells that entered the next phase despite considerable DNA damage can become cancerous and eventually form a tumor, which, in my opinion and most likely the opinion of others, will be groundbreaking for cancer research.

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