Mitosis – BioQuakes

Tag: Mitosis

The most common cause of hearing loss is the damage and loss of cells that grow the hairs inside the inner ear. These cells are aptly named cochlear hair cells. Repetitive exposure to loud environments, such as construction zones, concerts, or military bases can damage these cells, which, until recently, were thought to be irreplaceable. Normally, these cells enter the G0 phase after initial development ends when the organism is mature, which makes them similar to the brain cells we learned about in class. When a cell is in the G0 phase, it is frozen in the cell cycle, so the cell does not proceed through mitosis. This means that once the organism is done growing, there is no replacement of the damaged cells, as no cells are dividing.

In the animal kingdom, however, these cells are known to regenerate. Birds and fish have a mechanism which relies on a gene called ERBB2. The artificial expression of this gene in mammals has also been proven to trigger cell growth in a trial led by Jingyuan Zhang, PhD. They found that activating the ERBB2 gene triggered a cascading series of cellular responses which made the active cochlear hair cells multiply as well as trigger stem cells to become cochlear hair cells.

The research found that the activation of the ERBB2 gene caused stem-cell like development through the expression of a few proteins. The most important protein to this process, SPP1, signals the CD44 receptor, which exists on cochlear hair cells. The theory is that because these receptors are triggered, they somehow promote mitosis in the cells. The promotion of mitosis, the process of cell division in the cell cycle, would mean that these cells could be reproduced and the damaged cells could be replaced by new cells.

When this process was tested in adult mice, this cascade happened as previously shown in growing mice, meaning that the possibility of the development of new cochlear hair cells is possible in mature mammals, it just needs to be stimulated correctly.

The next step in the research is to determine whether or not these new cochlear hair cells are functioning mechanically. I don’t know about you, but I would maybe not stop wearing my earmuffs to use a jackhammer if I were you.

Researchers Discover Hacking Enzymes as New Cancer Treatment

By almoschetto

On March 15, 2023

In Student Post

We all know that mutations occurring in the synthesis of our cells lead to cancer, whether that be via ultraviolet light radiation, the inhalation of cigarette smoke over a long period of time, or otherwise. But how do these mutations actually occur, and if modern science knows that much, why can’t scientists step in before the mutation occurs in the cell and stop the creation of a cancerous one altogether? While the answer to this is evidently easier said than done, researchers such as Szymon Barcawz, Rahul Bhomick, Malgorzata Clausen, Marisa Dinis, Masato Kanemaki, Ying Liu, Katrine Lundgaard, and Wei Wu have found a way to limit the success of cancer-yielding cell mutations.

In this study titled, ‘Mitotic DNA Synthesis in Response to Replication Stress Requires Sequential Action of DNA Polymerases Zeta and Delta in Human Cells,’ researchers studied the replication process of cells, also known as mitosis, in human body cells (all human cells except gametes, sex cells). In order to understand the study fully, a few biological concepts should be covered first; For starters, the activation of the oncogene in relation to developing cancer. ‘Oncogene’ is simply a term for a mutated cell which turns cancerous. The activation of such creates disorder to cells going through mitosis called DNA replication stress, the name of which essentially reveals its effect: when genetic material is being synthesized under these conditions, it is extremely difficult for the mitotic cell to correctly replicate, causing faulty, under-replicated DNA regions (UDRs) to be built. Since DNA replication is completed in the S phase of interphase, which technically is before the commencement of mitosis in a cell; enough genetic material needs to be available for the cell to split in order for it to be replicated. Therefore, if UDRs are going to occur in a cell, they are created during this time.

However, our cells have developed clever adaptations to attempt to fight this type of cellular mistake. The strategy includes performing “‘unscheduled’ DNA synthesis in mitosis (termed MiDAS) that serves to rescue under-replicated” genetic material (Barcawz et al.). In studying this cellular defense mechanism, these researchers have discovered how exactly cells make up for a faulty S phase (the phase which copies DNA during mitosis) utilizing DNA gap-filling mechanisms (REV1 and Pol ζ) and DNA polymerases (group of enzymes) whose sole purpose is to replicate unfinished genomes (Pol δ). The study’s main goal, however, was to reveal which of these polymerases was the most crucial in the “rescuing” of under-developed genetic material, which were not, and which were not really necessary at all.

The researchers were most interested in studying POLDI (a subunit of Pol δ), REV 1, and REV 3 / REV 7 (both subunits of Pol ζ). These are all different polymerases whose main job is to “[promote] the bypass of damaged DNA sites” (Barcawz et al.). Each one works to solve a different issue within DNA replication that could lead to a mutation. For example, a TLS polymerase called Pol ζ4 is better at “bypassing bulky regions” of genetic material than the others (Barcawz et al.); this can be defined as Pol ζ4’s ‘role.’

A crucial realization in this study was that the polymerases Pol ζ and Pol δ may actually be switching roles at some point within the rescuing process by switching their subunits, which we defined earlier as POLDI, and REV3 / REV 7. But, this still doesn’t answer the question of whether or not all the aforementioned polymerases are essential in the process of fixing mutations in the copying of genetic material during mitosis.

The study at hand was successful at answering this question. It found that POLDI, REV1, and REV 3 are crucial to MiDAS, while REV7 is not at all. Additionally, it was discovered that POLDI and REV1 colocalize with another substance (FANCD2) in mitosis, which reveals how they both indeed play a role in the ‘rescue’ of under-replicated regions” (Barcawz et al.).

However, something unexpected about REV1 was also discovered. While it was found to be useful in mending UDRs in conjunction with POLDI and FANCD2, it actually does more harm than good: When REV1 was removed from the rescuing process in a situation where all the cell’s defense mechanisms failed at stopping the synthesis of a cancer cell, cancer cells were much less likely to survive in the human body. This suggests that it is very possible for a new and effective way to treat cancer to be the inhibition of the presence of REV1 polymerase.

In the coming years, if the inhibition of REV1 is found to be possible and turns out to be a promising way of preventing cancer cells from surviving in the body, we could be looking at a groundbreaking advancement to modern medicine and the world of cancer treatment as we know it changing forever.

Real image of cancer cell under a microscope.

Haven’t You Heard? Hearing Loss Could Be Reversible!

By deukaryota

On March 5, 2023

In Student Post

Hearing loss is a problem that affects almost a fifth of the world’s population, can cause feelings of isolation, and is closely correlated with dementia. Unfortunately, despite these drastic numbers and the fact that hearing loss can greatly worsen one’s quality of life, there is no way to reverse the effects of hearing loss. Or is there?

Neuroscientists at the Del Monte Institute for Neuroscience at the University of Rochester Medical Center believe they may have come up with just the solution. The most common cause of hearing problems is the damage of cochlear hair cells in the ear, which detect sound waves and allow mammals to hear. Sound wave detection from inner cochlear hair cells make up about 95% of the auditory nerve’s signal to the brain, and outer cochlear hair cells amplify sound vibrations. However, although mammals are unable to regenerate these cells, fish and birds can, allowing them to fix any hearing loss that they may encounter.

With this new study, the scientists discovered that the activating the ERBB2 growth gene, a gene that allows cochlear hair cell growth in birds and fish, triggers “a cascading series of cellular events by which cochlear support cells began to multiply and activate other neighboring stem cells to become new sensory hair cells.”

Furthermore, the scientists tested cells with/without the ERBB2 growth gene in mice, and they found that cells with the ERBB2 gene stimulated stem cell-like growth by inducing the expression of many proteins. One such protein was SPP1, which signals through the CD44 receptor, a receptor found in cochlear hair cells. This response signals mitosis, a process that we learned about in AP Biology, which is the process by which cells duplicate and, thus, grow.

The cell cycle, or the cycle of processes of a cell’s life, consists of four main phases: gap 1 (cell growth), synthesis (DNA replication), gap 2 (cell growth & organelle duplication), and cell division. In order for a cell to advance onto the next phase of the cycle, it must first pass checkpoints that affirm that the cell has completed the previous phases and is ready to move on. However, for cells that do not grow regularly, such as neurons and cochlear hair cells, they enter a phase between gap 1 and synthesis, called gap 0. In this phase, cells exit the regular cell cycle and cease to duplicate unless they receive a signal to do otherwise. This is why the SPP1 protein causes cell growth: because it gives the cochlear hair cells the signal to exit the gap 0 phase, continue on with the cell cycle, and duplicate, allowing the recovery of hearing.

Growth of the cochlear hair cells would allow mammals, including, eventually, humans, to regain their hearing after suffering from hearing loss. Scientists plan to continue researching and experimenting with this newfound information and hope to one day use this knowledge to reverse hearing loss at any stage of a person’s life. Just think about someone you know who has hearing loss: a grandparent? An uncle? A friend? Or maybe even you? This new research about the ERBB2 gene could heal the way they listen to music, watch TV, have a conversation, and live their everyday life.

The epigenome can be effected by pollution

By ethanelab

On February 16, 2022

In Student Post

The epigenome is a lesser known part of the study of genetics. It consists of the parts of the genome which are not part of the DNA, for example transcription factors and the accessibility of different sections of the chromatin. DNA in the cell is wrapped around proteins called histones. The wrapping of DNA around these histones are also a factor which controls which parts of the DNA are read into proteins. Furthermore, DNA methylation is an important regulatory factor. The addition of methane groups to DNA makes it impossible to read, effectively shutting off the gene that is methylating.

The epigenome is unique because it can be changed significantly in response to external stimuli. In a way, it is the body’s way of altering DNA on the fly, without actually altering the genetic code. The epigenome can also plays a role in cell differentiation. In class, we discussed how all cells have identical genetic code, passed down from one cell to another. All cells start the same and eventually change into all the different types. The epigenome helps to control exactly which parts of the genome are expressed. It is the epigenome which controls which parts of the genetic code are expressed.

However, the epigenome is still passed down hereditarily and down cell lines. As cells divide through mitosis or meiosis, the epigenome is passed down to the daughter cells. This combination of constant adaptation and persistence through generations make the epigenome an essential part of the body’s function. The combo also makes the epigenome a key part of how the body can be changed for a significant period of time by negative stimuli. These effects can even span generations and have been shown to effect the course of evolution.

Recently, scientists at the University of Liverpool have demonstrated exposure to pollution in water fleas has effects that last over 15 generations. When exposed to a pollutant for a period of 7 months, which encompasses 15 generations of fleas, scientists observed increased rates of DNA methylation. When transferred back to clean water, the scientists found that DNA methylation remained the same. Thus, the pollution permanently damaged the epigenome of the fleas.

Harnessing the Power of Regeneration

By rayceptor

On February 15, 2022

In Student Post

You at one point might have wished for this superpower after a broken bone. This ability to regenerate is natural to some animals like salamanders and starfish. Recently researchers did the unthinkable; they were able to regenerate a limb for our small amphibian friend.

Even though you may think that we don’t have regenerative powers, we have the ability to heal from a cut. However, we do not have the ability to regenerate an arm or a leg like a starfish. Instead, when we lose an arm, our body uses scar tissue to cover it. This is a very common mechanism in a lot of animals to prevent blood loss and bacterial infection.

Researchers at Tufts and Harvard universities worked together to develop a 5 drug cocktail that is used to regenerate their limbs, bones, and nerves instead of just simply clotting it. In their experiment, the animal being tested is the African clawed frog. There are 5 drugs in this process and a silk protein gel. First, the researchers put 5 drugs and the gel in the silicone wearable bioreactor dome that is attached to the frogs’ limbs. Once the drugs are in contact with the stump, the drugs stop the inflammation while also inhibiting collagen production. The importance of stopping collagen production is that it prevents scarring so the researchers can attempt to regrow the limb. The rest of the drugs encourage the growth of nerve fibers, blood vessels, and muscle that makes the limb function as a normal limb. The most amazing thing about this process is that the frog only needs to wear the silicone wearable bioreactor dome for 24 hrs and only be exposed to the drugs once; this will kickstart an 18-month journey of regeneration.

A Diagram showing the Interphase, Prophase, Prometaphase, Metaphase, Anaphase, and Telophase in Mitosis.

To understand how regeneration is happening, it is crucial to understand the process called mitosis. Mitosis happens when the cell is not in the interphase. If the cell passes the G1, G2, and mitosis checkpoint mitosis and cytokinesis will happen. Mitosis starts as a diploid cell with double-stranded Chromosomes but ends with cytokinesis, resulting in 2 genetically identical daughter cells that are diploid but single-stranded. After this process, the cell will go back to the interphase and G1 phase where the cell grows preparing for its next mitosis cycle. Mitosis is crucial for regeneration since it produces millions of cells in the frog’s body for a new limb to grow. With successful testing on amphibians, Michael Levin, a researcher on this project, said that they will “be testing how this treatment could apply to mammals next.”

This advancement in medical technology only serves to bring hope to future advancements like limb regeneration of human embryos. With so many people’s lives that can be changed for the better, I cannot wait for the future where we fully harness the power of biology. What do you think about this technology, and do you have ideas for other applications? Are there any downsides that you see?

ITS ALIVE!!! Scientists bring their creation to life.

By clalvincycle

On November 7, 2021

In Student Post

Cells are the basic units of life, but now scientists found a way to take matters into their own hands and actually create their own Frankenstein of cells. Scientists first created a single-celled organism with only 473 genes five years ago. Unlike the most recent cellular innovation, this simple cell grew and divided into cells of strange and unusual shapes and sizes. In an attempt to fix this, scientists identified 7 genes that when added to the cell, cause them to divide into perfectly uniform shapes. The J. Craig Venter Institute (JCVI), the National Institute of Standards and Technology(NIST), and the Massachusetts Institute of Technology(MIT) Center for Bits and Atoms all together can be accredited with this success.

How Was It Done?

The first cell with a synthetic genome was created in 2010 by the scientists at JCVI. Rather than building a cell from scratch, they started with cells from a simple bacteria called mycoplasma. The DNA already in those cells were destroyed and replaced with computer designed DNA. Thus lead to the first ever organism on Earth to have an entirely synthetic genome. It was named “JCVI-syn1.0”. Since then scientists have been working on stripping it down and reaching its minimum genetic components. Now scientists added 19 genes into this cell(including the 7 genes needed for proper cell division) and call it JCVI-syn3A. This cell variant also has fewer than 500 genes(a human cell has about 30,000). To find those 7 genes the JCVI synthetic biology group, led by John Glass and Lijie Sun, constructed multiple variants by adding and removing genes. NIST had to observe and measure the changes under a microscope. The difficulty here lay in observing the cells while they were alive, which made imaging them harder because of how small and fragile they were. Even the smallest of force could rupture them. Strychalski and MIT co-authors James Pelletier, Andreas Mershin and Neil Gershenfeld designed a microfluidic chemostat to remedy this. The article by NIST best describes this as a “sort of mini-aquarium where the cells could be kept fed and happy under a light microscope”. They discovered two known cell division genes, ftsZ and sepF, a hydrolase of unknown substrate, and four genes that encode membrane-associated proteins of unknown function, were all required together for cell division. As we learned in AP Bio, organelles like mitochondria and chloroplasts are also autonomous. That simply means that they are self replicating similar to this man-made cell.

The ability to create synthetic cells could lead to potential cells that produce drugs, foods and even fuels. Others can detect disease and the drugs to treat it all while being inside your body. It’s amazing to think that humans are capable of creating synthetic life on a molecular level. One can only hope that this power is used for good in the future. Do you believe that what these scientists are doing is ethical or is “playing God” tampering with forces unknown?

BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: Mitosis

Attention all Concert Attendees: Hearing Loss Is Potentially Reversible

Researchers Discover Hacking Enzymes as New Cancer Treatment

Haven’t You Heard? Hearing Loss Could Be Reversible!

The epigenome can be effected by pollution

Harnessing the Power of Regeneration

ITS ALIVE!!! Scientists bring their creation to life.

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