The bacteria in our gut make thousands of tiny, previously unidentified proteins that could shed light on human health and advance drug development, Stanford researchers have found.
Your body is a wonderland. A wonderland teeming with trillions of bacteria, that is. But it’s not as horrifying as it might sound. In fact, there’s mounting evidence that many aspects of our health are closely intertwined with the composition and hardiness of our microscopic compatriots, though exactly how is still mostly unclear.
Now, researchers at the Stanford University School of Medicine have discovered that these microbial hitchhikers — collectively known as the human microbiome — are churning out tens of thousands of proteins so small that they’ve gone unnoticed in previous studies. The proteins belong to more than 4,000 new biological families predicted to be involved in, among other processes, the warfare waged among different bacterial strains as they vie for primacy in coveted biological niches, the cell-to-cell communication between microbes and their unwitting hosts, and the critical day-to-day housekeeping duties that keep the bacteria happy and healthy.
Because they are so small — fewer than 50 amino acids in length — it’s likely the proteins fold into unique shapes that represent previously unidentified biological building blocks. If the shapes and functions of these proteins can be recreated in the lab, they could help researchers advance scientific understanding of how the microbiome affects human health and pave the way for new drug discovery.
A paper describing the research findings was published Aug. 8 in Cell. Ami Bhatt, MD, PhD, assistant professor of medicine and of genetics, is the senior author. Postdoctoral scholar Hila Sberro, PhD, is the lead author.
‘A clear blind spot’
“It’s critically important to understand the interface between human cells and the microbiome,” Bhatt said. “How do they communicate? How do strains of bacteria protect themselves from other strains? These functions are likely to be found in very small proteins, which may be more likely than larger proteins to be secreted outside the cell.”
But the proteins’ miniscule size had made it difficult to identify and study them using traditional methods.
“We’ve been more likely to make an error than to guess correctly when trying to predict which bacterial DNA sequences contain these very small genes,” Bhatt said. “So until now, we’ve systematically ignored their existence. It’s been a clear blind spot.”
The fact that she found thousands of new protein families definitely surprised us all.
It might be intimidating for the uninitiated to think too deeply about the vast numbers of bacteria that live on and in each of us. They account for far more cells in and on the human body than actual human cells do. Yet these tiny passengers are rarely malicious. Instead, they help with our digestion, supplement our diet and generally keep us running at our peak. But in many cases, it’s been difficult to pick apart the molecular minutiae behind this partnership.
Bhatt and her colleagues wondered if answers might be found in the small proteins they knew were likely to wiggle through the nets cast by other studies focusing on the microbiome. Small proteins, they reasoned, are more likely than their larger cousins to slip through the cell membrane to ferry messages — or threats — to neighboring host or bacterial cells. But how to identify and study these tiny Houdinis?
“The bacterial genome is like a book with long strings of letters, only some of which encode the information necessary to make proteins,” Bhatt said. “Traditionally, we identify the presence of protein-coding genes within this book by searching for combinations of letters that indicate the ‘start’ and ‘stop’ signals that sandwich genes. This works well for larger proteins. But the smaller the protein, the more likely that this technique yields large numbers of false positives that muddy the results.”
A big surprise
To tackle the problem, Sberro decided to compare potential small-protein-coding genes among many different microbes and samples. Those that were identified repeatedly in several species and samples were more likely to be true positives, she thought. When she applied the analysis to large data sets, Sberro found not the hundreds of genes she and Bhatt had expected, but tens of thousands. The proteins predicted to be encoded by the genes could be sorted into more than 4,000 related groups, or families, likely to be involved in key biological processes such as intercellular communication and warfare, as well as maintenance tasks necessary to keep the bacteria healthy.
“Honestly, we didn’t know what to expect,” Bhatt said. “We didn’t have any intuition about this. The fact that she found thousands of new protein families definitely surprised us all.”
The researchers confirmed the genes encoded true proteins by showing they are transcribed into RNA and shuttled to the ribosome for translation — key steps in the protein-making pathway in all organisms. They are now working with collaborators to learn more about the proteins’ functions and to identify those that might be important to the bacteria fighting for space in our teeming intestinal carpet. Such proteins might serve as new antibiotics or drugs for human use, they believe.
“Small proteins can be synthesized rapidly and could be used by the bacteria as biological switches to toggle between functional states or to trigger specific reactions in other cells,” Bhatt said. “They are also easier to study and manipulate than larger proteins, which could facilitate drug development. We anticipate this to be a valuable new area of biology for study.”
The Latest on: Small proteins
via Google News
The Latest on: Small proteins
- Faster modeling of interactions between ligands and proteinson November 29, 2019 at 6:59 am
A computational method for simulating the interaction between small molecules and proteins has been enhanced by an all-RIKEN team. This improvement promises to boost the speed and accuracy of ...
- NNTox: Gene Ontology-Based Protein Toxicity Prediction Using Neural Networkon November 29, 2019 at 2:22 am
Such cases happen for GO terms that are highly specific for toxins but only appear in annotation of a small number of proteins, thus not much helpful for the classification for many proteins in the ...
- UCLA scientists discover link between a protein and human blood stem cell self-renewalon November 27, 2019 at 7:41 pm
Other recent studies have identified small molecules -; organic compounds that are often used to create pharmaceutical ... The next steps for the researchers include determining what proteins and ...
- Scientists sheds light on small protein and its role in immune responseon November 27, 2019 at 1:50 pm
A chemical tag works by attaching to a protein to modify and regulate its activity. This way, the body has control over the expressed proteins. Ubiquitin is a small regulatory protein that is found in ...
- Big data and tiny proteins: shining a light on the dark corners of the gut microbiomeon November 27, 2019 at 3:14 am
In 2019, there have been substantial advances in our understanding of the gut microbiome. Key developments include an improved gut-on-a-chip system, a search for small proteins produced by the ...
- Protein Bar Market Growing Trends and Demands Analysis forecast 2019 to 2024on November 26, 2019 at 11:56 pm
The protein bar market was valued at USD 837 million in 2016. The Protein Bar market is highly competitive and consists of a number of major players: The Kellogg Company, General Mills, Inc., Mars, ...
- A protein tag to study the immune systemon November 26, 2019 at 9:57 am
Central is ISG15, a small protein with a role in the immune system. With the newly developed method, scientists can now identify and study proteins tagged with ISG15, allowing them to unravel its many ...
- 11 Reasons You Should Use Grass-Fed Whey Protein Powderon November 26, 2019 at 5:11 am
5. Unlike plant-based protein powders, grass-fed whey protein powder contains higher levels of BCAAs. BCAA stands for branched-chain amino acids. These are a small class of amino acids which all share ...
- Small rise in heart attack protein linked to increased risk of early deathon November 20, 2019 at 6:00 pm
An analysis of patients’ heart data has shown that even a small increase in a protein linked to heart attacks is linked to an increased risk of death. Clinicians use troponin testing, alongside other ...
- Even a small spike in a protein linked to heart attacks may TRIPLE your risk of an early deathon November 20, 2019 at 4:01 pm
Even a small spike in a heart attack-related protein may raise the risk of a premature death, scientists say. Data from 250,000 people showed having raised troponin levels tripled the odds of death ...
via Bing News