AP Biology class blog for discussing current research in Biology

Tag: #breakthrough

Are We One Step Closer To Eradicating Cancer?

Could you imagine if the scientists of today were able to produce a 100% percent effective treatment of all cancers? Researchers at the Children’s Hospital of Philadelphia (CHOP) have made a discovery that brings us one step closer. They had a breakthrough in the treatment of neuroblastoma, an aggressive solid cancer often found in children. When neuroblastoma is discovered in a patient’s nervous system, it is disguised so the immune system won’t attack it. The researchers have found that with the help of engineered CAR-T cells, treatment is possible for some leukemias and solid cancers, and hopefully every cancer in the future. T cells created in your body come from the thymus and have the sole purpose of floating around your body until they recognize a foreign antigen on the surface of a cell. They then get to work killing the host cells and activating other immune cells. Cytokines are released, creating a cell-mediated immunity. But because cancer cells do not appear as foreign to our immune systems, they are able to grow unchecked and can kill the patient. CAR-T cells are made from the patient’s own T cells and are “re-engineered” to see certain proteins on the surface of a cancer cell as foreign. When the CAR-T cells are searching for a cancer cell, they locate fragments of the proteins which are normally used as indicators through peptides on the major histocompatibility complex(MHC). The CAR-T cell then attacks cancer and hopefully kills the cancer cell. Neuroblastoma has proven difficult to cure with immunotherapy due to its low MHC levels. Neuroblastoma is a tumorous cancer that is most commonly found on the adrenal glands, but it is classified as an aggressive tumor due to its ability to metastasize. It is driven by modifications of gene expression that advance uncontrollable tumor growth.

CAR T-Cell Therapy

This recent advances in CAR-T therapy have led to breakthroughs in the treatment of leukemia, but the CHOP researchers are focused on neuroblastoma. Neuroblastoma presents a tricky challenge of how to connect CAR-T cells to destroy the cancer cell. The reason for this problem is that most of the proteins that the cell requires for survival and the growth of the tumor are inside the nuclei or the cell itself. After much research, they discovered peptides on the surface of the cell that can be targeted by peptide-centric chimeric antigen receptors (PC-CARS), activating the immune response to destroy the tumor. This is very similar to the receptor-mediated endocytosis we have studied in class. Two cells come together by recognizing indicators on the outside of the cell. Pushing through all the obstacles presented by the difficulty of locating and connecting with a neuroblastoma cell, the researchers at CHOP wanted to ensure that the CAR-T cells they sent into a patient’s body did not attach to similar peptides that exist in normal tissue, to avoid cross-reactivity. To do this, the researchers got rid of the MHC molecules present on the neuroblastoma cell to determine which peptides were present and at what population levels. They used a genomic database to do this. To pinpoint a perfect CAR-T cell, they filtered the peptides against the database of MHC peptides on normal human tissues, thus destroying any CAR-T that targeted a peptide with a parent gene from normal tissues. The final peptide discovery was an unmutated peptide of neuroblastoma cells that comes from the PHOX2B, which is a neuroblastoma dependency gene. They created a PC-CAR that was targeted to attack cells with this peptide on its surface. They discovered that not only does it locate the cancer cell, but it is able to do so with patients of more diverse genetic lineages. After this discovery, the researchers decided to first test their theory on mice, to prove that the PC-CAR can completely destroy the neuroblastoma tumors while not attacking normal cells in the mouse.

This subject is very important to me, as I have had family members pass from cancer. My father’s work in biopharmaceuticals has imparted a deep understanding of cancer. Many long car rides to sports games listening in on conference calls has not only given me a grander understanding of the world of business but also how it can relate to science and beyond. This discovery is vital to the continuation of the world facing all the diseases and struggles that come with life.


Advancements in Molecular Imaging May Further Human Knowledge

As we’ve learned throughout unit one, protein shape and structure are pivotal for deciding the protein’s function inside of the cell. Some proteins serve as enzymes to speed up chemical processes, while others serve as antibodies to protect against infectious diseases. Some are hormones, others provide structural support. What all of these proteins have in common is their amine group and carboxyl group which are both bonded to the central carbon, or alpha carbon; consisting of hydrogen, carbon, nitrogen, and oxygen, all proteins seemingly possess the same traits. But not all proteins are the same, in fact, there are twenty different amino acids which all pay tribute to the variable R group. Yet proteins are far more complex than just their variable R group. Proteins are able to reshape and undergo complex transformations that drastically alter their function inside the cell. These complexities, along with outdated technology, have created a substantial lapse of knowledge in this field, and scientists are in dire of a better understanding of the intricacies of protein structure.

Amino Acid Structure

Taking on the challenge of creating cutting-edge technology, a group of scientists stationed at the University of North Carolina Medical School discovered a new methodology to capture live-time imagery of unique protein shape and structure. This technologically advanced technique is being coined the ‘Binder Tag,’ which, “allows researchers to pinpoint and track proteins that are in the desired shape or “conformation,” and to do so in real-time inside living cells” (UNC Health Care).

The group of scientists, led by Ph.D. Klaus Hahn and Ph.D. Timothy Elston understood that they would be attacking a “fundamental challenge” of molecular imagery; this being that working molecules inside of cells are unable to be photographed because light from standard microscopes bends irregularly around particles inside the cell, creating a nearly impossible image to render. The ‘Binder Tag’ method avoids these limitations by inserting a molecule that has received a ‘tag’ into a protein, and then a separate molecule binds to the tag once the protein undergoes some type of formation alteration. Assuming the process is done correctly, researches are able to effectively image the precise location of tagged molecules over time, documenting real-time changes in the protein shapes.

Main protein structure levels en Furthermore, “a technique called FRET (Förster resonant energy transfer), which relies upon exotic quantum effects, embeds pairs of such beacons in target proteins in such a way that their light changes as the protein’s conformation changes” (UNC Health Care). However, FRET has its own limitations, such as the fluorescent beacon may be too weak to track live protein dynamics.

Hopefully, this method can be further experimented within the scientific community so we are able to better understand the complex, dynamic world of protein structure.




Cracking the Code one Gene at a Time

Cells are one of the most important objects in the human body, yet scientists still have yet to truly understand the underlying mechanics. Recently researchers have observed how RNA transcription occurs in real, live cells. For the longest time scientists have observed RNA transcription extracellularly. Until now they have only been able to observe how RNA polymerase 2, a DNA copying enzyme, and other enzymes “by breaking cells apart and measuring the activity… outside the cellular environment.”


The molecules involved in RNA transcription have been studied profusely, but only frozen in time. Now we can use “a highly specialized optical microscope” to watch how RNA polymerase copies DNA into mRNA. Researchers then labeled certain molecules with a tag so that they glowed when looked at. An issue with this method, though, is that there are so many of these molecules in the nucleus that if we were just to examine the reactions after adding the fluorescent tag, we would just have a glowing nucleus. The scientists have combated this by suppressing the signals from other reactions. This, along with the ultra-sensitive microscope allows us to focus on one gene and transcription occurs for it.

Through this new technique, we now have a much more detailed and intricate picture of how DNA, RNA, and enzymes function in transcription. This process can be replicated for many more reactions and will help us understand bounds more about ourselves and how we truly work.

I am personally very excited to see what new concepts and techniques will be discovered from this breakthrough. Genetics is the future of biology and using this to crack the code is one step closer to curing many genetic diseases. Combining this with other genetic breakthroughs like CRISPR is a cause for excitement in the future of biology. If you have any other ideas about why this could be useful please comment below.


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