Category Archives: Popular Science

LIFE-SAVING IMPROVEMENTS To Blood Transfusions

Posted on April 10, 2020 by | Leave a comment

Have you ever ended up in the hospital and needed a blood transfusion? Well, that’s about to get a whole lot easier for people everywhere! An article published by Nature Microbiology in June 2019 by Dr. Stephen Withers, studied a new method in converting type A blood to the universal type O blood using bacteria found in the human gut! [1] 

A team led by Dr. Stephen Withers at the University of British Columbia has developed a method which would eliminate the need for blood-type compatibility, reducing the risks of blood transfusions.  

What are blood types? 

There are 8 different blood types, and before these findings, these blood types were not all compatible with each other. Each blood type can only receive from other specific types.  

In human bodies, there are 8 types of red blood cells. These types are determined by two factors: Blood Groups and Rh Factors. 

We have 4 different blood groups: A, B, AB and O, different blood groups carry different signals (see Image 1).O-type cells do not carry any signals.

 Similarly, Rh-positive red blood cells carry another signal, and Rh-negative cells carry nothing. Blood groups and Rh factors are combined, so that we have blood types such as A positive, O negative, etc.

Image depicting the different signals on red blood cells. Created by Eric Ding using PowerPoint.

If we transfuse  O negative cells, which do not carry any signals, they can be recognized by anyone with any type of blood. 

 However, if we transfuse A positive red blood cells to a patient with AB negative blood, the immune system can recognize the triangle signal, but not the rectangular signal. The body will consider A positive red blood cells as enemies and attack them. This reaction can be fatal.

This problem has existed since blood transfusions were first scientifically achieved, and scientists have been looking for a solution for just as long. It turns out the solution was hiding right under our noses; inside our stomachs, to be specific!

The findings

Inside the human gut are thousands of microscopic bacteria which we use to digest food and convert it into energy. As it turns out, these bacteria are very good at safely interacting with the human body in helpful ways.

The researchers removed these bacteria through human faeces and found they could be used in exactly the way they were hoping. “Why would they be looking in our stomachs for this solution?” you might ask.

 The Withers group were on a hunt for a special kind of protein called an enzyme. Enzymes are produced by the body with a very specific task, and that task varies based on what the body wants it to do.

 Since our gut has the ability to process blood and turn it into energy, Withers and his team decided to see if these enzymes could be harnessed for their research.  As it turns out, they were completely correct.

An enzyme interacting with a specific molecule (known as the substrate) and cutting it into two different products. Modified from Wikipedia Commons.

The group screened more than 20,000 samples to find two enzymes that were particularly good at cutting the signal on A-type blood leaving us with O-type blood. These were removed from the body and tested on real red blood cells.  

The researchers discovered that the enzymes could efficiently cut the specific part of the A-type blood, essentially leaving us with type O red blood cells.

 These two types of enzymes were 30 times more efficient than previous methods, which means we only need a tiny amount of these enzymes to convert A, B, and AB types of red blood cells to O type red blood cells.

Impacts

In January 2020, the American Red Cross announced that it has a ‘critical’ shortage of type O blood. In the United States and Canada alone, 4.5 million patients need blood transfusions every year.[2] 

This high demand means that oftentimes, the supply cannot meet the demand.

 With this new discovery, incompatible blood types can be made compatible. This would increase the supply of compatible blood, which means more people can be helped.

While the process has been completed in the lab, it has yet to be scaled up to convert massive amounts of blood at a time.  This may take some time to accomplish. 

However, countless people will be helped and countless lives will be saved. And if one thing is for certain, it’s that blood donations will forever be easier.

References
  1. Rahfeld, P., Sim, L., Moon, H., Constantinescu, I., Morgan-Lang, C., Steven, J. H., Kizhakkedathu, J. N., Withers, S. G.; An enzymatic pathway in the human gut microbiome that converts A to universal O type blood. Nature Microbiology. 2019, 1475-1485.
  2. Community Blood Bank of Northwest Pennsylvania and Western New York. 56 facts about blood. https://fourhearts.org/facts/ (accessed March 22, 2020)

– Griffin Bare, Eric Ding, Chantell Jansz

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Posted in Biological Chemistry, Chemistry News, Popular Science

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Life-saving improvements to blood transfusion

Posted on March 30, 2020 by | Leave a comment

An article published by Nature Microbiology in June 2019, studied a new method in converting type A blood to the universal type O blood using bacteria found in the human gut! [1] A team led by Dr. Stephen Withers at the University of British Columbia has developed a method which would eliminate the need for blood-type compatibility, reducing the risks of blood transfusions.  

There are 8 different blood types, and before these findings, these blood types were not all compatible with each other. Each blood type can only receive from other specific types.  When doctors are going to transfuse blood to patients, they need to match the type of blood to one that can safely match with the patient’s blood type. If they don’t, the body will not know how to handle the new type of blood. This can cause blood vessels to rupture, which can be fatal.

This problem has existed since blood transfusions were first scientifically achieved, and scientists have been looking for a solution for just as long. It turns out the solution was hiding right under our noses; inside our stomachs, to be specific!

Inside the human gut are thousands of microscopic bacteria which we use to digest food and convert it into energy. As it turns out, these bacteria are very good at safely interacting with the human body in helpful ways. The researchers extracted these microorganisms through human faeces and found they could be used in exactly the way they were hoping.

         “Why would they be looking in our stomachs for this solution?” you might ask. The Withers group were on a hunt for a special kind of protein called an enzyme. Enzymes are produced by the body with a very specific task, and that task varies based on what the body wants it to do. Since our gut has the ability to process blood and turn it into energy, Withers and his team decided to see if these enzymes could be harnessed for their research.  As it turns out, they were completely correct.

An enzyme interacting with a specific molecule (known as the substrate) in the body.[2]

The group screened more than 20,000 samples to find two enzymes that were particularly good at cleaving the A-type blood. These were extracted and tested on real red blood cells and found that the enzymes could efficiently cleave a specific part of the A-type blood, essentially leaving us with type O red blood cells. These two types of enzymes were 30 times more efficient than previous methods, which means we only need a tiny amount of these enzymes to convert A, B, and AB types of red blood cells to O type red blood cells.

Image depicting the difference between blood types A, O, and B. The image shows that removing the yellow square in A type blood, is the same as O type blood. Modified from [1].

In January 2020, the American Red Cross announced that it has a ‘critical’ shortage of type O blood. In the United States and Canada alone, 4.5 million patients need blood transfusions every year.[3] This high demand means that oftentimes, the supply cannot meet the demand. With this new discovery, incompatible blood types can be made compatible. This would increase the supply of compatible blood, which means more people can be helped.

While the process has been completed in the lab, it has yet to be scaled up to convert massive amounts of blood at a time.  This may take some time to accomplish. However, it is impossible to quantify exactly how many people this new method will help, or even how many lives it will save. One thing is for certain, the world of blood donations will forever feel the impact of these findings.

References
  1. Rahfeld, P., Sim, L., Moon, H., Constantinescu, I., Morgan-Lang, C., Steven, J. H., Kizhakkedathu, J. N., Withers, S. G.; An enzymatic pathway in the human gut microbiome that converts A to universal O type blood. Nature Microbiology. 2019, 1475-1485.
  2. Western Oregon University: Chemistry. CH450 and CH451: Biochemistry – Defining Life at the Molecular Level. Chapter 6: Enzyme Principles and Biotechnological Applications. https://wou.edu/chemistry/courses/online-chemistry-textbooks/ch450-and-ch451-biochemistry-defining-life-at-the-molecular-level/chapter-7-enzyme-kinetics/ (accessed Mar 21, 2020)
  3. Community Blood Bank of Northwest Pennsylvania and Western New York. 56 facts about blood. https://fourhearts.org/facts/ (accessed March 22, 2020)

– Griffin Bare, Eric Ding, Chantell Jansz

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The Key to Treating Pneumonia can be Found in Soil?

Posted on March 27, 2020 by | Leave a comment

Can it really be that simple? Can the answer really be in the ground beneath our feet?

Source: Soil Science Society of America

Discovery of a gene cluster commonly found in soil-dwelling bacteria may be the key to treating anaerobic bacterial infections such as appendicitis and pneumonia. Researchers Jason B. Hedges and Prof. Dr. Katherine S. Ryan from the University of British Columbia have isolated the antibiotic compound azomycin from a biosynthetic gene cluster found in the bacterium Streptomyces cattleya.

With this information they believe it can lead to engineering bacteria to produce a new line of antibiotics.

What is a gene cluster?

The term gene cluster is moreso semantics to describe a group of genes that share a common phenomenon.

Originally, azomycin was isolated from a similar bacterium Streptomyces eurocidicus back in 1953 and became the blueprint to synthetic nitroimidazoles. 

“Nitroimidazoles are one of the most effective ways to treat anaerobic bacterial infections”,[1] Hedges writes in his 2019 study. The most commonly used nitroimidazole, metronidazole, is an antibiotic used to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis.[2] It is also on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system.[3]

Figure 1: Molecular Structure of Nitroimidazole. Source: Sigma Aldrich

Despite its use in antibiotics for over 60 years, the incidence of nitroimidazole resistance in anaerobes remains low, making it an essential component of the antibiotic arsenal. [1,4]

Since the isolation of azomycin back in 1953, synthesis of nitroimidazoles were limited to synthetic routes, most commonly involving reactions of an imidazole with nitric acid and sulfuric acid. 

Using bioinformatics, however, in 2019 Hedges and Ryan were able identify a biosynthetic gene cluster in the same bacterium that makes penicillin,[5] Streptomyces cattleya. They were able to find that this gene cluster containing azomycin is widely distributed among soil-dwelling actinobacteria and proteobacteria.

Because of this they theorize that azomycin and other nitroimidazoles may be important factors in ecology.

What are bioinformatics?

Bioinformatics is the science of collecting and analyzing complex biological data such as genetic codes. As an interdisciplinary field of science, bioinformatics combines biology, computer science, information engineering, mathematics and statistics to analyze and interpret the biological data

In addition to the isolation of azomycin in a gene cluster, Hedges and Ryan were able to perform in vitro analysis in order to understand the enzymatic steps that take the primary protein L-arginine to become azomycin. 

Source: Washington Post

Their work opens the door to biocatalytic methods to synthesize azomycin and other nitroimidazoles. They believe this discovery can “lead to the possibility of engineering bacteria to produce nitroaromatic compounds”.[1]

In other words, this may lead to stronger antibiotics immune to drug resistance.

References

Hedges, J. B.; Ryan, K. S. In Vitro Reconstitution of the Biosynthetic Pathway to the Nitroimidazole Antibiotic Azomycin. Angewandte Chemie International Edition 2019, 58 (34), 11647–11651.

The American Society of Health-System Pharmacists. Archived from the original on 6 September 2015. Retrieved 31 July 2015.

World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization

David I. Edwards, Nitroimidazole drugs-action and resistance mechanisms I. Mechanism of action, Journal of Antimicrobial Chemotherapy, Volume 31, Issue 1, January 1993, Pages 9–20, https://doi.org/10.1093/jac/31.1.9

Kahan, JS; Kahan, FM; Goegelman, R; Currie, SA; Jackson, M; Stapley, EO; Miller, TW; Miller, AK; Hendlin, D; Mochales, S; Hernandez, S; Woodruff, HB; Birnbaum, J (Jan 1979). “Thienamycin, a new beta-lactam antibiotic. I. Discovery, taxonomy, isolation and physical properties”. The Journal of Antibiotics. 32 (1): 1–12

-Adrian Emata

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Posted in Analytical Chemistry, Biological Chemistry, Chemistry News, Organic Chemistry, Popular Science

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Origin of the Coronavirus

Posted on March 24, 2020 by | Leave a comment

Recently, the outbreak of new coronavirus has seriously affected people’s lives in countries and even around the world. New coronaviruses can be transmitted through air and contact. Symptoms include fever, cough, and difficulty breathing. In order to completely solve this infectious disease, it is very important to find the primary case.

Source:https://www.heywood.org/education/covid19-coronavirus-updates

Initially, Chinese scientists believed that the source of the virus was the South China Seafood Market in Wuhan, China. When people eat wild animals that contain the virus, the non-pathogenic version of the virus jumps from animal hosts to humans and then evolves into the current pathogenic state in the population. For example, the RBD structure of some coronaviruses from pangolins, armadillo mammals found in Asia and Africa, is very similar to SARS-CoV-2. Coronavirus from pangolin may have been transmitted to humans either directly or through an intermediary host such as a civet or ferret.

Source:http://m.cyol.com/content/2020-03/05/content_18413469.htm

Most people in this epidemic believed that this new coronavirus should be derived from flying mammals such as bats. Many people also criticized them, and even many people targeted the bats directly, thinking that those who eat bats Caused the disease. However, this is actually questionable. Although it is possible that bats can directly infect humans, so far, most of the time, bats are not the direct source of infection but are adapted to spread to humans through the intermediate source of infection. This can be seen from the case report published in the top medical journal “The Lancet”.

Source:https://news.sky.com/story/how-did-coronavirus-start-scientists-tackle-the-conspiracy-theories-11959500

Researchers from institutions such as the Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences recently published a paper in the form of a preprint, saying that they analyzed the genomic data of 93 new coronavirus samples in 12 countries on four continents and found that they contained 58 haplotypes, which are related to the South China Seafood Market The associated patient sample haplotypes were H1 or its derivative types, while the more “older” haplotypes such as H3, H13, and H38 came from outside the South China seafood market, confirming that the new crown virus of the South China seafood market was transmitted from elsewhere In perspective.

Source:https://meaww.com/coronavirus-did-chinese-officials-downplay-extent-of-deadly-wuhan-outbreak-in-early-stages

Finding an “index case” is equivalent to finding a weapon that can cut the epidemic from the source. But in the long history of humans fighting the epidemic, few “index cases” have been found. On the one hand, the timeline of the index case and first case are not necessarily the same, which makes the process of tracing like a needle in a haystack. In addition, the chain of evidence tracking “index case” is difficult to finalize and will always be repeatedly overturned and readjusted.

To this day, the epidemic of AIDS, Ebola, SARS and so on has never clearly identified the “index case” in the strict sense. From the perspective of the development of the global epidemic, it is still of great significance to curb the development of the epidemic while researching and developing effective drugs and vaccines and controlling the development of the epidemic in a timely manner. However, the new Coronavirus may be the same as AIDS and SARS. There is no way to accurately find the first human it infected.     

Yicheng Zhu

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Posted in Biological Chemistry, Popular Science

Biosynthetic Pathway Found to Synthesize Anaerobic Antibiotics!

Posted on March 23, 2020 by | Leave a comment

Fig 1. Image of Azomycin. source

Scientists found the biosynthetic pathway to the Nitroimidazole Antibiotic Azomycin. A steppingstone towards the revolution of anaerobic bacterial infection treatments.

Scientists from the University of British Columbia found the biosynthetic pathway to the Nitroimidazole antibiotic Azomycin. The enzymatic mechanism from L-Arginine to Nitroimidazole has now been proved and present to the public. Their formal paper was published online on July 17th, 2019. Nitroimidazole is an essential component for the modern antibiotics, it is crucial to know its synthetic pathway for further pharmaceutical studies. The result of their study set the stage for further development of important anaerobic antibiotic Azomycin.

What is it? Why do we need to know about this?

Nitroimidazole is an essential antibiotic specifically to treat anaerobic bacterial infections. They are widely used to treat diseases such as Amoebiasis, Parasitic infections, skin infections, diarrhea and so on. The low redox potential of anaerobic bacteria cells allowed nitroimidazole to act as the electron sink and form the radical species. The resultant radical species would induce the bacteria cells’ death by damaging their DNA. Antibiotic is the most powerful “weapon” to fight against bacterial infections. However, according to the World Health Organization, there are more than 700000 people die every year due to antibiotic resistance. Despite the several decade’s usages of Nitroimidazole antibiotics, the drug resistance of it still remains low relatively. Thus, Nitroimidazole antibiotics are increasingly used to treat multi-drug resistant bacteria as well.

 

Previous research established that L-Arginine is converted to azomycin by 2-aminioimidazole. They determined that the intermediate of the reaction is 4-hydroxy-2-ketoarginine (2). Furthermore, they also observed the accumulation of pyruvate(3) side products and 2-aminoimidazole(5) from the intermediate(2). However, the actual enzymatic synthetic pathway has not been determined detailly yet. Jason and Katherine in the research group determined that PLP-dependent enzymes, RohP,RohR,RohQ and RohS plays esstential role in the catalytic pathway of the reaction. Researchers examined the in vitro activity of RohP, RohR, RohQ and RohS. They put in these enzymes separately and stepwise to different reactants. For example, in order to test whether RohR could catalyze a retro-aldol cleavage of 2 into 3 and guanidinoacetaldehyde (4), they added purified RohR instead of RohP. Then according to activity analysis and also the mass spectrum, the result shows that RohP yields a bigger portion of 2.

Fig 2. Reaction scheme from L-Arginine to Nitroimidazole. Source

Antibiotics are the most powerful “weapon” to kill bacteria in modern pharmaceutical studies. As early as in the 20th century, the observation of penicillin saved millions of people injured in the World War. Yet, the enormous benefits of antibiotics cause the consequences of drug-resistance. Azomycin, consider as a low-resistance antibiotic, it is crucial to understand its enzymatic reaction mechanism. Reaction mechanism allows scientist to have a more detail interpretation of the synthesis. It is crucial to find the catalytic cycle of the reaction, in order to allow scientists to develop and derive further study.

The study done by Jason and Katherine at the University of British Columbia provides the public with a steppingstone in future nitroimidazole anti-biotics study. Their study expanded people’s knowledge of the biosynthetic pathway to nitro-compounds. It also makes bacteria engineering to produce nitroaromatic compounds possible. This study will open the new door in enzymatic synthesis and biochemistry synthesis.

Cited article:

Hedges, J. B.; Ryan, K. S. In Vitro Reconstitution of the Biosynthetic Pathway to the Nitroimidazole Antibiotic Azomycin. Angewandte Chemie International Edition 2019, 58 (34), 11647–11651.

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A new technique that can cut gene of RNA virus?

Posted on March 23, 2020 by | Leave a comment

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), referred  as gene magic scissors, is a kind of tool that scientists can find in the immune system of bacteria to edit genes in other organisms is undoubtedly a revolutionary technology, which has greatly improved the efficiency of gene editing work.

In recent years, CRISPR-based gene screening has successfully helped scientists identify genes that play a key role in sickle cell anemia, cancer immunotherapy, lung cancer metastasis, and many other diseases.

However, the scope of these gene screenings is limited, and they can only edit and target DNA. This brings many restrictions since in many regions of the human genome, DNA may not work as a target; for some other organisms, such as RNA viruses including coronaviruses and influenza viruses.

On March 16, an important paper was published in the journal Nature-Biotechnology, reporting a new CRISPR screening technology that can target RNA. In the paper, researchers describe an enzyme called Cas13 that can be used for CRISPR screening techniques that target RNA instead of DNA.

Cas13 traveling along RNA (Source)

Cas13 is a type VI CRISPR enzyme, which is a class of RNA targeting proteins with nuclease activity that have only been discovered in recent years. They can knock out target genes without altering the genome. This property makes Cas13 a promising therapeutic tool that can affect gene expression without permanently altering the genome sequence.

Using Cas13, the researchers obtained an optimized platform for large-scale parallel genetic screening of human cells at the RNA level. Using this gene screening platform, researchers can learn about RNA regulation from all aspects and the functions used to identify non-coding RNAs (RNA molecules that cannot encode proteins).By targeting thousands of different sites in human RNA transcripts, they have developed a machine learning-based predictive model that can quickly identify the most effective Cas13 guide RNA (gRNA).

For example, one of the findings is about which regions of gRNA are more important when identifying target RNAs. They used thousands of gRNAs containing one, two, and three single bases that didn’t match the bases of the target RNA, and identified a key “seed” region that guides and targets CRISPR Mismatches between them are extremely sensitive. This is a very useful discovery for gRNA design.

Since a typical human cell can express approximately 100,000 RNAs, accurate targeting of Cas13’s predetermined targets is critical for screening and therapeutic applications. The “seed” area not only deepens our understanding of Cas13 off-target, it can also be used to study next-generation biosensors to more accurately distinguish between close relative RNA species.

Recently, researchers also applied their gRNA prediction model to the raging coronavirus Sars-CoV-2. We know that COVID-19 is caused by this coronavirus that contains RNA instead of DNA genome. The researchers said that using this new model, they have identified the best gRNAs for future detection and treatment.

Overall, the new study increased the data points of mammalian cells in Cas13 by more than two orders of magnitude, which is of great significance for advancing genomics and precision medicine.

 

-Xinyue Yang

-Posted on Mar. 23, 2020

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Life Saving Improvements to Blood Transfusions

Posted on March 23, 2020 by | Leave a comment

Previously thought impossible, researchers have found a way to create O type blood from other blood types. Since O is a universal donor, these other blood types can now be used as universal donors, potentially saving countless lives.

A team of biochemists from the University of British Columbia, lead by doctor Stephen Withers, have turned A positive and A negative type blood into the universal O type blood. These findings were published in June of 2019 in the journal “Nature Microbiology.”[1]

Before these findings, the 8 major blood types were not all compatible with each other. This meant that if a blood transfusion were needed for a patient, a specific type of blood maybe be needed, with no other type working.

A chart of what blood types can donate or receive other blood types.[2]

This problem has existed since blood transfusions were first scientifically achieved, and scientists have been looking for a solution for just as long. It turns out the solution was hiding right under our noses; inside our stomachs, to be specific!

Inside the human gut are thousands of microscopic bacteria which we use to digest food and convert it into energy. As it turns out, these bacteria are very good at safely interacting with the human body in helpful ways. The researchers extracted these microorganisms through human feces and found they could be used in exactly the way they were hoping.

“Why would they be looking in our stomachs for this solution?” you might ask. The Withers group were on a hunt for a special kind of protein called an enzyme. Enzymes are produced by the body with a very specific task, and that task varies based on what the body wants in to do. In the below picture, notice how the enzyme matches perfectly the substrate. This is because enzymes are made for specific purposes, and only match specific molecules in the body. Since our gut has the ability to process blood and turn it into energy, Withers and his team decided to see if these enzymes could be harnessed for their research.  As it turns out, they were completely correct.

An enzyme interacting with a specific molecule (known as the substrate) in the body.[3]

Future Impacts

 In the United States and Canada alone, 4.5 million patients need blood transfusions every year.[4] This high demand means that often times, the supply cannot meet the demand. With this new discovery, more blood types are compatible, which means more people can be helped.

While the process has been completed in the lab, it has yet to be scaled up to convert massive amounts of blood at a time.  This may take some time to accomplish. However, it is impossible to quantify exactly how many people this new method will help, or even how many lives it will save. One thing is for certain,  is that the world of blood donations will forever feel the impact of these findings. 

 References:

  1. Rahfeld, P., Sim, L., Moon, H., Constantinescu, I., Morgan-Lang, C., Steven, J. H., Kizhakkedathu, J. N., Withers, S. G.; An enzymatic pathway in the human gut microbiome that converts A to universal O type blood. Nature Microbiology. 2019, 1475-1485.
  2. Canadian Blood Services. Do You Know Your Blood Type? https://blood.ca/en/blood/donating-blood/whats-my-blood-type (accessed March 21, 2020)
  3. Western Oregon University: Chemistry. CH450 and CH451: Biochemistry – Defining Life at the Molecular Level. Chapter 6: Enzyme Principles and Biotechnological Applications. https://wou.edu/chemistry/courses/online-chemistry-textbooks/ch450-and-ch451-biochemistry-defining-life-at-the-molecular-level/chapter-7-enzyme-kinetics/ (accessed Mar 21, 2020)
  4. Community Blood Bank of Northwest Pennsylvania and Western New York. 56 facts about blood. https://fourhearts.org/facts/ (accessed March 22, 2020)

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Making Different Sugars with Enzyme (Pac-Man) In Our Body

Posted on March 23, 2020 by | Leave a comment

Although eating too much sugar can lead to health complications, a normal intake of sugar has its benefits. This is because sugars take part not only in many cellular activities as an energy source but also in cell-cell communication as a communicator. In 2019, a research team led by Dr. Stephen Withers at the University of British Columbia made different sugars by using enzymes (Pac-Man-like molecules) in bacteria. This finding enables the building of many sugars that are commonly hard to find in nature.

What are sugars?

All sugars are made of hexagonal building blocks as shown in red in Figure 1. Two common building blocks are glucose and fructose. To make different sugars with only two common building blocks, we can vary the number and arrangement of the building blocks. For example, cellulose has three long threads that are arranged almost parallel to each other. In contrast, starch has one long thread that adopts a helical structure.

Now we know that different sugars can be made by varying the kinds of building blocks, the numbers of building blocks and the arrangements of building blocks. What we haven’t talked about is how the building blocks are linked. There are two issues with linking the building blocks. First, building blocks are much smaller than our cells. Getting two building blocks together is as hard as fishing a needle from the Pacific Ocean. Besides, getting two building blocks together takes time because they prefer to be alone. How can our mother nature solve these problems to keep us alive?

Figure 1. Sugars are built differently. Some sugars are longer and more complex than others. Source: riasparklebiochemistry

Here comes the rescue…Pac-Man in the cells!

The illustrations of enzymes are like Pac-Man. However, different from Pac-Man that eats any “food” in different shapes, enzymes recognize different substrates and those substrates only! Because of this substrate-enzyme specificity, linking two building blocks together is much easier. As shown in Figure 2, the enzyme will attract two specific building blocks, making them closer to each other and eventually join.

Figure 2. Different enzymes recognize different substrates. Source: Wikipedia

Besides, enzymes can speed up the “hugging” process between the substrates (building blocks), making the formation of a long sugar favorable.

Figure 3. Enzymes speed up reactions. Source: pinimg.com

Manipulation of enzymes to build different sugars for cell-cell communication

Knowing that enzymes have many advantages, Dr. Wither and his team looked for enzymes that speed up the linkage of sugar building blocks in E. Coli, bacteria that live inside our digestive tracts. They chose eight enzymes out of the 175 sugar-specific enzymes in E. Coli. These eight enzymes were the most specific to the sugar building blocks they were interested in. However, after further investigation, the researchers found that the enzymes helped speed up the breakage of the linkage(s) between sugar building blocks instead of the formation of the linkage(s).

Figure 4. Some enzymes speed up the breakage of linkages while others speed up the formation of linkages.
Source: Canstock.com

To solve this problem, the researchers reverse-engineered these enzymes from speeding up breakage to speeding up linkage by changing parts of the enzymes. Now different sugars can be made! As mentioned above, cell-cell communication relies on sugars. This is because two cells adhere via the interaction between extracellular sugars and specific cell-surface receptors. Once these cells adhered to each other, they can talk to each other about their internal cellular condition/environment and trigger a corresponding response. This has great implications in triggering an immune response to a viral attack. By engineering more sugars on the surface of the cells, cells in our immune system can more quickly talk to each other and fight off infection.

 

Journal Source:

Armstrong, Z.; Liu, F.; Chen, H.-M.; Hallam, S. J.; Withers, S. G. Systematic Screening of Synthetic Gene-Encoded Enzymes for Synthesis of Modified Glycosides. ACS Catalysis 2019, 9 (4), 3219–3227.

-Pricia Ouyang

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Novel method of converting any blood type to the universal O

Posted on March 23, 2020 by | Leave a comment

A journal article published by Nature in June 2019, studied a novel method in converting type A blood to the universal type O blood using bacteria found in poop! The Withers’ research group at the University of British Columbia used the DNA of bacteria found in the faecal samples to develop this efficient method.

HOW ARE BLOOD TYPES CLASSIFIED?

There are four main blood types: A, B, AB, O.

Blood type is determined by the type of antigens and antibodies present in the blood. Antibodies are part of your body’s defense system, if they sense germs (or any other foreign substance) they alert your immune system which stimulates a biological response to destroy said germs.

Antigens are proteins that are directly attached to red blood cells that are used to identify blood as A, B, AB or O. Antigens are also attached to foreign substances, and antibodies use them as indicators that a substance does not belong in the body. Figure 1 shows how antibodies interact with antigens.

Figure 1: Image of antibody interacting with an antigen. Obtained from Wikipedia commons.

For example, if you have type A blood then your red blood cells will have A antigens. However, your blood will have type B antibodies. This means that the immune system will attack any substance with B antibodies – including type B blood. This explains why individuals who get blood transfusions can only accept their same blood type, unless it is the universal type O.

Universal type O blood doesn’t have any antigens so anyone can accept O blood as their antibodies will not attack the red blood cells. Figure 2 shows the different blood groups and how they are classified.

Figure 2: Image of different blood types depicting what antigens and antibodies they contain. Obtained from Wikipedia commons.

RESULTS OF THE STUDY

Figure 3 shows an in depth depiction of the difference in antigens between the blood groups.

Figure 3: In depth image depicting the different constituents of antigens on type A, O and B blood. Obtained from journal article “An enzymatic pathway in the human gut microbiome that converts A to universal O type blood”

The researchers of this study, synthesized  enzymes from the bacterial DNA found in poop. Enzymes are a type of protein that aid in the reactivity of a reaction, essentially meaning they help a reaction occur faster by breaking down substances. Figure 4 demonstrates how enzymes break down substances known as substrates.

Figure 4: Image depicting how enzymes break down substances into two products. Obtained from Wikipedia commons.

In this case, the researches synthesized an enzyme that break down the bond labelled ‘3-α’ in type A and B blood cells (Figure 3). Once this bond is broken down, you are left with type O blood. The enzyme that Dr. Stephen Withers group identified, breaks down this bond 30 times faster than the previous candidate.

WHAT ARE THE IMPLICATIONS?

In January 2020, the American Red Cross announced that it has a ‘critical’ shortage of type O blood.

With this new method, hospitals and relief organizations, such as the American Red Cross, can convert type A and B blood to the universal O. It is vital that hospitals and relief organizations have a constant supply of O blood in case they need to do blood transfusions without knowing the blood type of the patient. It could also completely eliminate the need for blood type compatibility, if the research leaves the lab.

This enzyme is 30 times faster and, thus, more efficient than the previous candidate. This means that less of this enzyme is required to convert the same amount of blood, drastically decreasing the cost of production.

Overall, not only is this new method interesting to the science community but is is also incredibly important to the healthcare system.

 

-Chantell Jansz

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Bacteria: Friend or Foe?

Posted on March 23, 2020 by | 1 comment

Did you know that not all bacteria is bad? In some cases, they cause diarrhea, stomach ulcers, and even intestinal diseases. However, what if I told you scientists have found a way to manufacture antibiotics that are used to treat these bacterial infections from bacteria themselves?

Scanning Electron Microscope view of bacteria. Retrieved from: NYTIMES

Dr. Jason Hedges and Dr. Katherine Ryan of the University of British Columbia took a look into finding new enzymatic pathways for synthesizing nitroimidazole, which is a component in the antibiotic, azomycin.

So what is the point of this whole process and why do we even want to use bacteria to synthesize antibiotics?

By finding more ways to develop antibiotics from bacteria, this improves our knowledge on biosynthetic pathways. This is beneficial not only for the scientific community, but for the public as well. As bacteria develop resistances to antibiotics over time, the discovery of new antibiotics would be able to treat more patients suffering from bacterial infections.

How is this done?

Now how could something that sounds so complex be done? Let us take a look at their process step-by-step.

Like all scientists do, background research was performed to see how previous scientists went about finding ways to develop antibiotics from bacteria. To do so, a bioinformatics search was performed. Bioinformatics is essentially ‘googling’ information about a certain topic, but in this case, they would be using a scientific database such as the National Centre for Biotechnology Information (NCBI).

A cryptic gene cluster was found in the bacterial strain Streptomyces cattleya. This along with various enzymes were the main points of interest. Their goal was to use L-arginine; a fundamental building block of proteins, and find a way to convert this into nitroimizadole (a component of the antibiotic, azomycin

Theoretically, a blueprint on how L-arginine would be converted to nitroimidazole was developed. However, experiments must be conducted to see if the pathway would work in real life, and not just on paper.

Figure 1 – Biosynthetic pathway towards nitroimidazole. Retrieved from: Hedges and Ryan, 2019

Through experimentation, the pathway as shown in figure 1 was deemed to have synthesized nitroimidazole successfully. The next step was to determine whether or not azomycin could be synthesized from Streptomyces cattleya. Unfortunately, they were unsuccessful in detecting any levels of nitroimidazole in the bacteria samples. They concluded that potentially a different molecule had been synthesized, or that this specific gene cluster is silent (inactivate).

Although Hedges and Ryan were unable to find a definitive pathway to synthesizing azomycin utilizing bacteria, their work was able to disprove aa few reaction schemes in the scientific community, allowing for further research to be conducted.

Science is not always about success. In science, you must fail in order to succeed. Their work provides a stepping stone into further scientific research such a finding other biosynthetic pathways in the synthesis of other antibiotics.

 

Literature Cited:

Hedges, J. B.; Ryan, K. S. In Vitro Reconstitution of the Biosynthetic Pathway to the Nitroimidazole Antibiotic Azomycin. Angewandte Chemie International Edition 2019, 58 (34), 11647–11651.

-Jackson Kuan

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