AP Biology class blog for discussing current research in Biology

Tag: quorum sensing

Chimeric Antigen Receptor T-Cell Therapy: Successful Research to Improve Cancer Treatments

Cancer is when abnormal cells divide without control and spread to other parts of the body through the bloodstream and lymph systems to cause illnesses. Immunotherapy is a type of treatment that utilizes a person’s immune system to battle diseases like cancer. Under the branch of immunotherapy, there is a specific therapy that has been recently improved upon.

Chimeric antigen receptor (CAR) T-cell therapy is a treatment that stimulates T-cells to fight cancer by editing them in the lab so they can be released into the body to find and destroy cancer cells. This treatment has been successful in treating certain types of hematologic malignancies but unsuccessful on solid tumors. Hematologic malignancies are cancers that begin in blood-forming tissues such as the bone marrow and in the immune system. Examples of cancers that can be treated with the CAR T-cell therapy include leukemia, lymphoma, and multiple myeloma.CAR T-Cell Therapy 

CAR stimulates macrophage phagocytosis function against tumor cells and its immunomodulation capacity. Scientists have already achieved success with this therapy in B cell leukemia/lymphoma but are still caught up on complications with solid tumors. The main challenge about solid tumors arise from its immunosuppressive tumor microenvironment. There is also a limited effect on infiltration into the dense extracellular matrix of the solid tumors.

In this type of therapy, the macrophages are the most important aspect of the success in treatment. Macrophages play a central role in the crosstalk between the adaptive and innate immune system. The immune system defends the body and marks pathogens and cancer cells for macrophages to fight and engulf. The researchers at Zhejiang University partnered with a researcher at the Fujian Medical University and The First Affiliated Hospital and Center for Stem Cell and Regenerative Medicine to study macrophage specific CARs and the development of EGFRvIII (epidermal growth factor receptor variant III) Targeting CAR-iMACs. The chimeric antigen receptors were further genetically engineered into induced pluripotent stem cell (iPSC) derived macrophages (iMACs) so that the CAR treatment was more effective toward solid tumors. The firefly luciferase gene (Ffluc) was discovered to promote the research through the bioluminescence signal response from tumor cells.

Macrophages were equipped with receptors called pattern recognition receptors (PRRs) through the discovery of the importance of bioluminescence cell signaling. The chimeric antigen receptor was then reprogrammed to contain Toll/IL-1R (TIR), a domain containing adapter inducing interferon β. The TIR-containing CAR is a novel engineered PRR that recognizes antigen associated molecular patterns and enables macrophages with antigen dependent polarization to be more pro-inflammatory to aid immune cell therapies in cancer.

Connection to AP Biology:

The chimeric antigen receptor T cell therapy has a great deal of connections to our AP Biology class.


CAR treats certain types of cancers, usually those in the blood-forming tissues. As we learned in AP Bio, cancers form when a cell does not properly divide and bypasses the checkpoints in the mitosis cycle. These abnormal cells don’t always become cancerous but they no longer follow the signals to stop dividing, causing masses that could one day become cancerous. 

Macrophages & Phagocytosis:

Macrophages and phagocytosis was something that we learned about in the first semester. Macrophages are specialized cells that are involved in pathogen detection so that phagocytosis can occur and destroy bacteria and other harmful substances.

Phagocytosis occurs when a cell engulfs solid things into the cell. We learned about phagocytosis along with pinocytosis and receptor-mediated endocytosis. In CAR therapy, phagocytosis occurs to engulf pathogens and cancer cells.

Bioluminescence:PanellusStipticusAug12 2009

In AP Bio, we did not directly learn about bioluminescence but we learned about cell communication and cell signaling. In bacteria, there is quorum sensing and it allows bacteria to share information about cell density and adjust gene expression. In bioluminescence bacteria, the power to produce light is controlled by quorum sensing. One bioluminescent bacteria cannot light up on its own, but when multiple bioluminescent bacteria gather together, quorum sensing signals for the “light” to shine once it senses enough of the bacteria together.


Bacteria May Not Be As Simple As We Once Thought

Bacteria biofilms are ubiquitous in our world, living in various conditions that allow bacteria to build up, such as sewer pipes or even our own teeth. New studies have shown that bacteria not only have intelligent systems for communication but also have the ability to remember things.

Biofilms are ancient, with evidence of biofilms dating back to 3.25 billion years ago. While they are able to grow on many different surfaces, these surfaces all share a commonality: they’re wet. Biofilms to humans are a cause 

of concern regarding our health since biofilms can grow on implanted medical devices, which can lead to infections. Bacterial biofilms can also cause infective endocarditis and pneumonia. Furthermore, bacteria that are within a biofilm are also more resistant to antibiotics and other disinfectants and are considered to be 1,500 times more resistant.

Grand Prismatic Spring

The Grand Prismatic Spring is probably the most popular biofilm, as the various bacteria biofilms give the spring its bright colors.

Biofilms have recently been recognized as an advanced community, with the discovery that biofilm cells are organized in intricate designs that plants and animals have been known to use. Süel, a UC San Diego Professor of Molecular Biology, states that this concept of cell patterning is much more ancient than they once thought. This new discovery opens the possibility that this segmentation of cells may go back to over a billion years, and was not just a new emergence from plants and animals.

As found through experiments and mathematical models, the study revealed that the biofilms involved used a “clock and wavefront mechanism,” which sophisticated organisms such as plants, flies, and humans use. A “wave” of nutrient depletion moves across cells, which dresses a molecular clock inside each cell that creates a pattern of distinct cell types as the biofilm expands and consumes nutrients. This breakthrough identified the circuit that the biofilm’s ability to generate community concentric rings of genetic patterns.

As seen in AP Biology, the formation of a biofilm is an example of Cell Communication. With unicellular organisms, they are able to communicate with each other to signal for the availability of food, identify mating types, or detect others for coordinated behavior. For bacteria, they utilize Quorum Sensing, in which they secrete small molecules that are detected by other bacteria. If they sense the population is close enough to perform group behavior, they will begin to do so.

This new discovery opens many doors to various research fields, due to the fact that biofilms are prevalent in our everyday lives. From medicine to the food industry to the military, these biofilm systems can be used to test and investigate the in-depth aspects of the clock and wavefront mechanism. Plants and vertebrate systems are harder to study, but bacteria aren’t because they “offer more experimentally accessible systems that could provide new insights for the field of development,” Süel states. 

Personally, I am very interested in how these studies are going to be used, specifically in a “military” field. Furthermore, do you think there is more groundbreaking information regarding bacteria that can help us put the pieces together for life before humans? Let me know in the comments below and thank you for your time!


Message Intercepted – Commence attack on bacteria!

Tevenphage – Photo credit to Wikimedia Commons

While experimenting, a group of scientists noticed that a A virus, VP882, was able to intercept and read the chemical messages between the bacteria to determine when was the best time to strike. Cholera bacteria communicate through molecular signals, a phenomenon known as quorum sensing, to check their population number.  The signal in question is called DPO.  VP 882, a subcategory of bacteria’s natural predator, the bacteriophage, waits for the bacteria to multiply and is able to check for the DPO.  Once there is enough bacteria, in the experiment’s case they observed cholera, the virus multiples and consumes the bacteria like an all-you-can-eat buffet. The scientists tested this by introducing DPO to a mixture of the virus and bacteria not producing DPO and found that that the bacteria was in fact being killed.

The great part about VP 882 is it’s shared characteristic with a plasmid, a ring of DNA that floats around the cell. This makes it easier to possibly genetically engineer the virus so that it will consume other types of bacteria. This entails it can be genetically altered to defeat other harmful bacterial infections, such as salmonella.

Ti plasmid – Photo credit to Wikimedia Commons

Current phage therapy is flawed because phages can only target a single type of bacteria, but infections can contain several types of different bacteria.  Patients then need a “cocktail” with a variety of phages, which is a difficult due to the amount of needed testing in order to get approved for usage.  With the engineering capability of using a single type of bacteria killer and the ability to turn it to kill bacteria, phage therapy might be able to advance leaps and bounds.

As humans’ storage of effective antibiotics depletes, time is ticking to find new ways to fight bacterial infections.  Are bacteriophages and bacteria-killing viruses like VP 882, the answers?

Virus VP882: Our Forgotten Spy to End our Bacteria Problem

The virus VP882, which had long ago sequenced in Taiwan as a part of a study of an outbreak of cholera, has now resurfaced and has the potential to make major waves in our addressing of the harmful bacteria. In recent years, biomagnification of harmful bacteria, in large part due to human waste, like Escherichia Coli and Vibrio Cholerae are having immediate and detrimental effects on our environment and in human health as well. For example, a significant amount of produce circulating in the United States has been contaminated with Escherichia Coli causing many to contract Shiga toxin-prducing E. coli infection (STEC) which, as according to the Centers for Diseases Control and Prevention (CDC), can causes “severe stomach cramps, diarrhea (often bloody), and vomiting”.

Our problem today is that the production of bacteria-specific responses to infection are difficult to produce and become costly as a result. Most of our anti-bacterials today target bacteria-made toxins, in order to restore affected G-Protein cell signaling function. Unfortunately, this treatment may negatively impact the integral human microbiome. An alternative way of countering bacterial infections is through use of phage therapy. This treatment is much more specific, bringing less harm to the host organism, and involves viruses to enter and reproduce in bacterial cells, eventually causing them to lyse, thus killing them. While objectively this process seems far superior than the current general treatment, too often the infective bacteria remains unknown, which as M.I.T. Professor Mark Mimee discusses in the Scientific American article on the VP882 virus, forces doctors to prescribe “a cocktails of different phages. But manufacturing cocktails and adhering to drug regulations is too expensive.” Then enters the VP882 virus.

The VP882 virus works just as most other bacteriophages: the virus uses bacteria as hosts for their reproduction, and cause them bacteria cells to lyse, after they have hijacked a given bacterium’s reproductive mechanisms. There are two things, though which make this virus special in the realm of bacteriophages. VP882 has the ability to sense bacterial cell communication and is a very simple structure, similar to a plasmid. This virus’s discovery can in part be credited to a coincidence. A student at Princeton, Justin Silpe, in his study of a molecule, DPO, which is integral in bacteria cell signaling, specifically quorum sensing, ran across this surprising virus which was sequenced in the presence of DPO. What he and his professor, Bonnie Bassler, found is that this virus, which was attacking cholera cells, was able to secretly calculate the optimal time to invade the bacteria (thus its many comparisons to a spy), by sensing a high quantity of DPO, which is a signal for when bacteria can begin their collective behavior, and possibly start a disease. What this means is that because of this ability to understand a bacteria’s quorum, they can most effectively counteract an infection.

In addition, upon further study, VP882 was found to be a very simple structure. This arguably the most important aspect of VP882. The virus is very similar to a plasmid, which can be easily modified and, thus accepted by a plethora of bacteria. This leads scientists like Bassler and Silpe to believe that VP882 can be modified to create an all-encompassing bacteriophage treatment, one which could be made cheaply and work far more effectively than general anti-bacterial treatments. Whether this is feasible still remains unknown, but in the time being, VP882 can be readily applied to neutralizing cholera in industrial wastewater without harming the natural microbiome, proving already the usefulness of this discovery.

Discharge Tube Releasing Cholera-filled Wastewater



Genetic Engineering on Gut Bacteria!?

E. coli on MAC – Photo credit to VeeDunn on flickr under Creative Commons License

Researchers at the Wyss Institute at Harvard University has successfully tested a genetically engineered signaling bacteria within a mouse’s gut. Having known that the many types of bacteria in the human gut can communicate through “quorum sensing” , researchers set to observe a particular type of quorum sensing, acyl-homoserine lactone sensing, which has not been observed in the mammalian gut. They wanted to test if using that particular type of signaling could create a genetically engineered bacterial information transfer system.

Using a strain of E. coli bacteria, they created two different colonies, each with a different genetic change: one was the “signaler”, it contained a copy of the luxl gene which produces a quorum-sensing molecule when activated, and the other was the “responder”, which contained a “cro” gene turning on a “memory element” in the responder.  This “memory element” expressed another copy the the pro gene, which allowed for the loop to continue, and the LacZ gene, which made the bacteria turn blue!

LacZ gene expression – Photo credit to Viraltonic on Wikimedia Commons under Creative Commons License

The researchers analyzed fecal samples of mice given signaler and responder E.coli and they were happy to see the signal transmission, blue coloring, was evident in the samples. This result meant that they had created a functional communication bacteria system in the mouse’s gut.

The researchers then repeated their experiment with a different type of bacteria, S. Typhimurium, as the “signaler” and E. coli as the “responder”, and they were pleased to see similar successful results.  They were able to successfully confirm that is possible to genetically engineer these communication circuits between different species of bacteria in the mammalian gut microbiome.

These tests are merely stepping stones for the bigger goal of creating genetically modified bacteria that will help humans in various different ways: detecting and or curing diseases, improving digestion, and so on. Isn’t it cool that something we barely realize is inside us has such a developed communication system that we might soon be able to cultivate more benefits from? What do you think would be some other benefits to be being able to genetically modify our gut microbiomes?



Bacteria may be more complex than we think

Photo by Wikimedia Commons

A common public misconception is that bacteria live alone and act as solitary organisms. This misconception, however, is far from reality.

Bacteria always live in very dense communities. Most bacteria prefer to live in a biofilm, a name for a group of organisms that stick together on a surface in an aqueous environment. The cells that stick together form an extracellular matrix which provides structural and biochemical support to the surrounding cells. In these biofilms, bacteria increase efficiency by dividing labor. The exterior cells in the biofilm defend the group from threats while the interior cells produce food for the rest.

While it has long been known that bacteria can communicate through the group with chemical signals, also known as quorum sensing, new studies show that bacteria can also communicate with one another electrically. Ned Wingreen, a biophysicist at Princeton describes the significance of the discovery; “I think these are arguably the most important developments in microbiology in the last couple years, We’re learning about an entirely new mode of communication.”

An entirely new mode of communication it is! Heres how it works:

Ion channels in a bacteria cell’s outer membrane allow electrically charged molecules to pass in and out, just like a neuron or nerve cell. Neurons pump out Sodium ions and let in Potassium ions until the threshold is reached and depolarization occurs. This is known as an action potential. Gurol Suel, a biophysicist at UCSD emphasizes that while the bacteria’s electrical impulse is similar to a neuron’s, it is much slower, a few millimeters per hour compared to a neuron’s 100 meters per second.

Photo by Chris 73 Wikimedia Commons

So what does this research mean?

Scientists agree that this revelation could open new doors to discovery. Suel says that electrical signaling has been shown to be stronger than traditional chemical signaling. In his research, Suel found that potassium signals could travel at constant strength for 1000 times the width of a bacteria cell, much longer and stronger than any chemical signal. Electrical signaling could also mean more communication between different bacteria. Traditional chemical signaling relies on receptors to receive messages, while bacteria, plant cells, and animal neurons all use potassium to send and receive signals. If these findings are correct, there’s potential in the future for the development of new antibiotics.

Learning about electrical signaling in bacteria has complicated our understanding of these previously thought to be simple organisms. El Naggar, another biophysicist at USC says, “Now we’re thinking of [bacteria] as masters of manipulating electrons and ions in their environment. It’s a very, very far cry from the way we thought of them as very simplistic organisms.”



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