BioQuakes

AP Biology class blog for discussing current research in Biology

Author: almoschetto

Exploring Multicellularity on Planet Earth

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On April 30, 2023

In Student Post

Billions of years ago, it is believed that some event—whether it be a meteor crash-landing on planet Earth, or a lightning strike creating amino acids and proteins—sparked the origin of life. From there, single celled organisms, like bacteria, made their home on our planet; and eventually, unicellularity became multicellularity. The reason behind this phenomenon, though, is what continues to be unknown. What really is the point of the majority of organisms being compiled of millions of cells, and not just one? 

Scientists at Lund University strive to answer this question. In order to do this, green algae from Swedish lakes were taken into their lab, as this specific botanic organism is extremely suitable for the goals of this experiment. For one, it is a eukaryote, which will allow researchers to gain insight on the evolution of all eukaryotes, in general. They are widely studied in the study of evolution because of their very apparent evolutionary process. There is a great amount of data to reveal that all eukaryotes have common ancestry, including the presence of double membranes, circular genomes, ribosomes, linear chromosomes, and more in all eukaryotic organisms. 

Another reason as to why green algae is such an appropriate fit for an experiment exploring the evolutionary characteristics of unicellular and multicellular organisms is that it is sometimes unicellular, other times starts off this way but then becomes multicellular, and the remaining types are always multicellular. This makes green algae the perfect candidate for an experiment such as this. Data from the environments of all these different cellularly-dense types of algae was collected and compared to one another. While doing this, scientists looked out for the adaptations promoted by the environments the algae were in, what conditions exactly promoted unicellularity or multicellularity, and why the form of life it encouraged was beneficial to the organism. 

Previously, it had been theorized by evolutionary biologists that multicellularity benefited organisms that utilized it, but the Lund University research team was shocked at the results they found from analyzing the environmental data of the algae: there were no benefits of living multicellularly for these organisms. A member of the study, Charlie Cornwallis, made the following comment on the experiment’s outcomes: “I was surprised that there were no benefits or costs to living in multicellular groups. The conditions that individual cells experience can be extremely different when swimming around on their own, to being stuck to other cells and having to coordinate activities. Imagine you were physically tied to your family members, I think it would have quite an effect on you.” 

At the conclusion of the study, Charlie Cornwallis made one final statement: “The results of this study contribute to our understanding of how complex life on Earth has evolved….The next time you walk along the shores of a lake rich in nitrogen just imagine that this fosters the evolution of multicellular life.”

Green algae under a microscope

Green algae under a microscope.

Is Nobel Prize-Winning CRISPR Technology as Sound as Scientists Say?

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On April 23, 2023

In Student Post

CRISPR—short for ‘clustered regularly interspaced short palindromic repeats’—is a nobel-prize winning scientific advancement in genetic modification technology. It was initially developed by Dr. Jennifer Doudna of Harvard University, and is based on the naturally occurring gene-editing system found in bacteria. Researchers now use this new method to modify the DNA of various organisms, potentially being able to make advancements in disease treatment, improving resilience of crops, correcting genetic defects, and more. 

CRISPR-Cas9 Editing of the Genome (26453307604)

To make an understatement, the introduction of CRISPR into the scientific community has been nothing short of groundbreaking, but researchers from Rice University have raised their own doubts about this seemingly miraculous technology, and whether or not it is as fool-proof as it’s presented to be. In response to this question, they have begun to lead an effort with a goal “to reveal potential threats to the efficacy and safety of therapies based on CRISPR-Cas9…even when it seems to be working as planned.” 

CRISPR-Cas9 was designed to treat sickle-cell anemia. In order to combat this disease, the technology works to edit large sequences in a patient’s DNA, therefore aiming to change their DNA and erase the aspect of it that makes them suffer from the illness. However, researchers have begun to fear that taking such a large step as this (erasing large portions of one’s DNA) is presumptuous, and could possibly yield dangerous, long-term effects, since this genetic modification CRISPR allows will only further spread throughout the patient’s body through stem cell division/differentiation. 

These fears mainly stem from the fact that scientists are not sure how DNA strands are able to rejoin after so many of their sequences have been cut out, and therefore, separated. However, bioengineer Gang Bao of Rice University has other concerns, as well: “large deletions (LDs) can reach to nearby genes and disrupt the expression of both the target gene and nearby genes.’”

Gene expression is a very complex process that occurs in the cells of all organisms, but which can be broken down into two major steps: transcription—”synthesis of RNA using information from DNA”—and translation—”synthesis of a polypeptide or protein using information in the mRNA.”  This process running smoothly is extremely important, as the ‘information from the DNA,’ or amino acid bases, need to be copied exactly without any mistakes, duplicates of bases, etc.. 

Bao also expresses another concern about CRISPR-Cas9: “‘you could also have proteins that misfold, or or proteins with an extra domain because of large insertions. All kinds of things could happen, and the cells could die or have abnormal functions.’”

With so many hypotheses at play, Bao and his research team knew they had to somehow figure out answers: they developed a technique called SMRT—’single molecule, real time’—that utilizes molecular identifiers to seek out and find accidental LDs, long insertions, and chromosomal rearrangements that are located at a Cas9 cutting site. To do this, a machine was used called the ‘LongAmp-seq’ (long-amplicon sequencing) to emphasize the presence of particular DNA molecules. This allows for the quantification of LDs and large insertions on a DNA strand. 

Researchers used streptococcus pyogenes as a medium. With this bacteria, they edited enhancers such as beta-globin (HBB), gamma-globin (HBG), and B-cell lymphoma/leukemia 11A (BCL11A), and genes such as PD-1 gene in T-cells of sickle-cell anemia patients. 

In testing these, they found incredible results: across the 3 enhancers and 1 T-cell gene, the average frequency of several thousand large DNA deletions averaged a whopping 20.025%. 

While it is unclear at this time whether Bao’s team’s discoveries will unveil consequences of genes modification by CRISPR technology, they state that they will work to “determine the biological consequences of gene modifications due to Cas9-induced double-strand breaks,” and look forward to testing if “‘these large deletions and insertions persist after the gene-edited HSPCs are [transplanted] into mice and patients.’

Researchers Discover Hacking Enzymes as New Cancer Treatment

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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.

Cancer cells

Real image of cancer cell under a microscope.

Can Enzymes Be the Solution to the Single-use Plastic Pollution Crisis?

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On December 21, 2022

In Student Post

Single-use plastic pollution, a massive issue that has been harming our planet’s environmental health for decades, might be able to be tackled with something as small as an enzyme.

Researchers Jen Dubois of Montana State University and John McGeehan of the University of Portsmouth have discovered enzymes that break down elements of single use plastic. These remarkable microbiological tools, called PETase and MHETase, have the ability to breakdown terephthalate polyethylene—one of the building blocks of (PET) plastic. 

So, how does it work? How do these enzymes essentially eat plastic?                       PET is a polymer, which is a mega-protein made up of many smaller molecules (monomers). With the help of PETase and MHETase, these enzymes break the plastic down into “chemical building blocks”: ethylene glycol (EG) and TPA. Evidently now, a problem arises that concerns where these byproducts of the enzyme’s activity can go next. Thankfully, EG is a product that is useful for many everyday items, such as being an ingredient in antifreeze solution used in cars. But researchers can’t tell the same story for TPA; There is essentially no use for a chemical like this outside of PET plastic. So, with inspiration from the mechanism that made this byproduct in the first place, the Portsmouth research team thought the creation or discovery of another enzyme could do the job of breaking down TPA in the same way as for PET plastic.

Researchers from Michigan State University did just that, and found a solution to the overwhelming amount of TPA byproduct from PETase/MHETase activity of breaking down PET plastic. TPADO, an enzyme that breaks down TPA byproducts, was introduced, and was soon found to have incredibly binding ability to TPA—so much so that its fit into the chemical is described as “a hand in a glove.” In other words, the active site, the groove on the surface of the TPADO enzyme, fits perfectly with its substrate, TPA, by matching its exact shape, charge, and type of relationship with water (either hydrophobic or hydrophilic). 

This groundbreaking research due to the collaboration of many researchers across several universities has revealed the long awaited light at the end of a very dark tunnel environmentalists call ‘the plastic crisis.’ With around 400 million tons of plastic discarded and then scoured all over the earth every year, the human race produces a weight of single-use plastic trash that is almost equivalent to the mass of the whole human population. But, with enzymes like PETase, MHETase, and now TPADO, modern science is now able to convert plastic waste into valuable molecular ingredients for other products, essentially minimizing waste in not only the plastic industry, but others, as well. 

Still, these researchers’ jobs are not done, and they know it. TPADO has been tested under powerful x-rays to show its exact shape and molecular structure and reveal its innerworkings. With information like this, the world of enzyme engineering can be improved to make artificial ones that are more efficient and more useful. 

So, something as small as enzymes can be the solution to the single-use plastic crisis we have here on planet earth? The answer is ‘yes’, thanks to modern science and dedicated researchers at the universities of Montana, Portsmouth, and Michigan State.

Plastic bottles for recycling

Image of single-use plastic waste.

Why Nearly Every Human on the Planet Has Contracted Covid-19

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On December 8, 2022

In Student Post

While some have only heard the term ‘Coronavirus’ starting in 2020, the drama around this type of infectious disease is not new. This type of virus brings on illnesses that you have most likely contracted long before the start of the pandemic in March of 2020. For example, the common cold. But of course, Coronavirus is not responsible for just that– they also bring on SARS (severe acute respiratory syndrome) and MERS (middle eastern respiratory syndrome). With SARS-CoV-2 being the virus that causes COVID-19,  this extremely contagious disease is, in fact, a strain of SARS. 

But if the Coronavirus has been around long before now and there are so many types of it, what makes SARS-CoV-2 special? The answer to this is its relationship with a particular enzyme, ACE-2, whose shape, function and location opens doors right up for COVID-19 to enter and infect our healthy cells. 

While other types of SARS also attached to this enzyme, the ingenious design of the SARS-Cov-2 protruding spike protein is what makes this virus particularly contagious; Throughout the evolution of this virus from other versions of SARS, the shape of their spike protein has become more refined and specific through compaction of its structure to better mimic the shape of the receptor dock of a naturally-occurring enzyme called ACE-2. This mutation allows the virus to strengthen the grip that they can have on human’s cells, making their infection rate much more high and effective. 

The function and location of ACE-2 also practically facilitates the infection of SARS-CoV-2 within us. These enzymes play a critical role in the renin-angiotensin system (infection-fighting system), and while this virus utilizes them as an entrance to the body as a means to infect, it is reducing the function of the very cells that are supposed to be fighting it. Additionally, this suppresses the rest of the functions of our immune system. 

In the human body, one way in which our immune system works is by the release of T lymphocytes, or T-cells, along with macrophages and monocytes to fight off infections. However, with SARS-CoV-2 having already hijacked ACE-2 at the time when T-cell release is activated, the immune system becomes dysfunctional; the three aforementioned immunity cells are released via a positive feedback loop in a much greater magnitude than usual/ than with other illnesses. Lastly, ACE-2 positive cells are present in over 70 types of our bodily cells, and are especially abundant in oral, nasal, and nasopharynx tissues, which are hot spot entrances for this virus (and many others).

With the involvement of just one enzyme within our bodies, SARS-CoV-2 throws all aspects of our immune system into a disarray.  With the many adaptations and evolutions of SARS viruses, infectious diseases such as these are just getting smarter and smarter each time they sweep through the human population.

Coronavirus. SARS-CoV-2

SARS-CoV-2 Spike Protein

Scientists Discover Super-Protein Involved in Gene Replication

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On October 24, 2022

In Student Post

For over 50 years, it has been believed all factors that control gene activation in humans were identified and known to scientists. However, researchers from the University of California San Diego and Rutger’s have proved this theory wrong. 

Collegiate professors, and now pivotal contributors to modern science Dr. Jia Fei and James Kadonaga, have discovered a new protein that is involved in the regulation of RNA polymerase. Called NDF (nucleosome destabilizing factor), this gene-building molecule not only unravels nucleosomes, but also “turbocharges” RNA polymerase as it works its way along the DNA strand, improving the synthesis of replicating RNA.

But that’s not all this protein has to offer: NDF has also been found to be in an array of species and organisms, ranging from yeast particles to mammals. This widespread presence suggests that NDF is an ancient factor in the process of gene activation, and has been here since the very beginning. 

NDF works by first interacting with nucleosomes in cells, and then goes on to facilitate transcription– in other words, to replicate strands of RNA. Enzymes called RNA polymerases then come into play, and copy the RNA via dehydration synthesis. This process includes removing oxygen molecules and hydroxides from each nucleotide to covalently bind them together, producing a waste product of water molecules and, finally, a copy of the RNA strand. 

While this newly discovered protein is crucial for the elongation of RNA strands in many organisms, it is especially abundant in humans. Kadanoga reports that it is “present in all [our] tissues,” particularly in stem and breast cells. This makes sense, as NDF has actually been linked to breast cancer; Abnormally high levels of this protein lead to hyperactivity in gene synthesization, which increases the chance of a mutation occurring, and thus cancer. 

With all the remarkable characteristics of NDF, it is crucial that scientists today continue to explore the capabilities and effects of this gene-activating protein, and use it as a basis for studying diseases and phenomenons that occur in the process of gene replication.

RNA recognition motif in TDP-43 (4BS2)

Depiction of RNA strand.

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