Tag Archives: UBC

LIFE-SAVING IMPROVEMENTS To Blood Transfusions

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

H2hox and Gallium: A Dynamic Duo in Medical Imaging

Not every molecule gets to find their best “partner” in life. Luckily in 2019, Dr. Chris Orvig and his team at the University of British Columbia constructed a partner molecule for Gallium to work with in medical imaging. They also determined that their creation has superior stability and binding ability compared to similar molecules currently being used.

THE NEW MOLECULE IN TOWN

The partner molecule is a chelating ligand known as H2hox. Let’s break down its name piece-by-piece to get a better understanding of what it does.

A ligand is a molecule that binds onto a metal ion such as iron (Fe3+) or copper (Cu2+). In the case of H2hox, the metal ion is Gallium (Ga3+ ).

The word chelating comes from the latin root word chela, which means claw. This is because chelating ligands have multiple points of attachment to a metal ion, similar to a crab’s claw, making them significantly stronger binders to metal ions.

Image sources (left to right): Research Gate, Wang et al..

THE DUO GETS TO WORK

H2hox is used in a form of medical imaging known as positron-emission tomography (PET). PET imaging is used to diagnose health issues related to the processes occurring inside our cells, such as cancer.

The main function of H2hox in PET imaging is to bind to radioactive Gallium ions, which aids in producing an image of a desired area or tissue inside the body.

To test how well H2hox worked together with its partner, Gallium, the researchers conducted a PET scan in mice. The group witnessed high stability of the dynamic duo within mice, and they observed that it was rapidly excreted from the mice, which is important for a decrease in side effects.

Furthermore, the ligand has a strong affinity to Gallium, such that only low amounts of ligand are needed to significantly bind to Gallium ions in just five minutes! As a result of the molecule’s advanced properties, H2hox surpasses any ligand currently used as a Gallium’s partner.

ALL IT TAKES IS 1 STEP

In the lab, H2hox is synthesized (made) in only one reaction and is easy to purify, unlike similar ligands which are synthesized over multiple labor- and resource- intensive steps. As a bonus, the chemicals used to make it are inexpensive and readily available.

To put this into perspective, it’s like baking a box cake versus baking a cake from scratch. The former is quite easy to do, while the latter is a lot harder and is more labour-intensive. Ease of manufacturing is a key feature because it determines the commercial success of the product.

THE FUTURE IS PROMISING

The combination of unprecedented properties and easy synthesis makes H2hox a launching-off point for the development of even better chelating ligands to improve the future of PET imaging. With H2hox being such an advantageous molecule for Gallium PET imaging, we cannot wait to see what else this dynamic duo has to offer the world.

Literature cited:

  1. Wang, X.; Jaraquemada-Pelaez, M. d. G.; Cao, Y.; Pan, J.; Lin, K.-S.; Patrick, B.O., Orvig, C. H2hox: Dual-Channel Oxine-Derived Acyclic Chelating Ligand for 68Ga Radiopharmaceuticals. J. Am. Chem. Soc. 2019, 58, 2275-2285

 

-Group 6 (Mark, Akash, Athena, Charles)

Life-saving improvements to blood transfusion

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