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
- African swine fever shows need for safer proteins, not supersized farmson October 17, 2019 at 11:00 am
The outbreak has already forced the closure of many small farms, and China's policies ... balancing consumption between meat and alternative sources of protein looks essential.
- 13 high-protein, high-fiber snack ideason October 17, 2019 at 10:38 am
we may get a small share of the revenue. READ MORE The line between snacks and meals is getting blurrier so it’s more important than ever to choose filling and nutritious options. Your best chance of ...
- Plexium Debuts With $28M and a New Take on Protein Degradation Drugson October 17, 2019 at 9:44 am
Even as researchers discover more links between specific proteins and human disease, it’s still hard to find small molecules or antibodies that can bind to those drug targets. San Diego biotech ...
- These 200-calorie, plant-based protein bars taste nothing like the chalky vegan bars you're used toon October 16, 2019 at 12:42 pm
TruWomen nutrition bars are made from natural, Plant Fueled ingredients. In addition to creating great tasting bars, the company supports women's empowerment.
- Animals Are Out, Alt Protein Is In—and It’s Cooking Up Some Unbelievable Creationson October 16, 2019 at 7:00 am
If the idea of chowing down on a lab-grown burger someday still sounds a little fantastical, then the following efforts to reimagine and redesign animal-free protein will seem out of this world. Let’s ...
- Is Whey Protein Powder Gluten-Free? How to Be Sureon October 16, 2019 at 5:38 am
If you buy something through a link on this page, we may earn a small commission. How this works. Whey is one of the most common types of protein used in protein powder, and it has many benefits. It’s ...
- Protein Expression Market Value is Expected to Reach $2.63 Billion by 2022on October 16, 2019 at 4:42 am
The European Medicines Agency has also introduced policies which include a provision to waive the scientific advice fee, which encourage more academic groups and small companies to propose candidates ...
- Nanosecond photochemically promoted click chemistry for enhanced neuropeptide visualization and rapid protein labelingon October 16, 2019 at 2:14 am
as demonstrated by its general applicability using a series of proteins with various lysine residues from multiple sample sources, with accumulated labeling efficiencies greater than 90%. For example, ...
- G-Protein Coupled Receptor (GPCR) Targeting Market Trends And Emerging Progress Challenges 2019-2026on October 15, 2019 at 8:13 am
The global G-Protein Coupled Receptor (GPCR) Targeting Market not only studies the top key players but also takes into consideration the role of the small and medium scale enterprises. Technological ...
- Cytotoxic T Lymphocyte Protein 4 Market 2019 | Business Strategies to Understand the Competitive Scenarioon October 9, 2019 at 12:18 pm
The global Cytotoxic T Lymphocyte Protein 4 Market not only studies the top key players but also takes into consideration the role of the small and medium scale enterprises. Technological advancement ...
via Bing News