Research could lead to clinical laboratory tests in service of precision medicine therapies to reduce a person’s susceptibility to being targeted by blood-sucking insects
Ever wonder why some people attract mosquitoes while others do not? Could biting insects pick their victims by smell? Scientists in California believe the answers to these questions could lead to new precision medicine therapies and clinical laboratory tests.
The research revealed evidence that some blood-sucking insects may identify their prey by homing in on the “scent” of chemicals produced by bacteria located in the skin microbiome of animals and humans.
This is yet another example of research into one area of the human microbiome that might someday lead to a new clinical laboratory test, in this case to determine if a person is more likely to attracts biting insects. If there were such a test, precision medicine therapies could be developed that change an individual’s microbiome to discourage insects from biting that individual.
Then, the clinical laboratory test would have value because it helped diagnose a health condition that is treatable.
“In these caves, I’d see all these different bat species or even taxonomic families roosting side by side. Some of them were loaded with bat flies, while others had none or only a few,” Lutz said in Phys.org. “And these flies are typically very specific to different kinds of bats—you won’t find a fly that normally feeds on horseshoe bats crawling around on a fruit bat. I started wondering why the flies are so particular. Clearly, they can crawl over from one kind of bat to another, but they don’t really seem to be doing that.”
The researchers suspected that the bacteria contained in the skin microbiomes of individual bats could be influencing which bats the flies selected to bite. The bacteria produce a distinctive odor which may make certain bats more attractive to the flies.
The type of fly assessed for the study are related to mosquitoes and most of them are incapable of flight.
“They have incredibly reduced wings in many cases and can’t actually fly,” Lutz explained. “And they have reduced eyesight, so they probably aren’t really operating by vision. So, some other sensory mechanisms must be at play, maybe a sense of smell or an ability to detect chemical cues.”
To test their hypothesis, the research team collected skin and fur samples from the bodies and wings of a variety of bat species located in various caves around Kenya and Uganda. They collected their samples at 14 field sites from August to October in 2016. They then examined the DNA of the bats as well as the microbes residing on the animals’ skin and searched for the presence of flies.
“The flies are exquisitely evolved to stay on their bat,” said Carl Dick, PhD, a professor of biology at Western Kentucky University and one of the study’s authors. “They have special combs, spines, and claws that hold them in place in the fur, and they can run quickly in any direction to evade the biting and scratching of the bats, or the efforts by researchers to capture them,” he told Phys.org.
“You brush the bats’ fur with your forceps, and it’s like you’re chasing the fastest little spider,” Lutz said. “The flies can disappear in a split second. They are fascinatingly creepy.”
Genetic Sequencing DNA of Bat Skin Bacteria
After collecting their specimens, the researchers extracted DNA from the collected bacteria and performed genetic sequencing on the samples. They created libraries of the bacteria contained in each skin sample and used bioinformatics methods to identify the bacteria and compare the samples from bats that had flies versus those that did not.
“How the flies actually locate and find their bats has previously been something of a mystery,” Dick noted. “But because most bat flies live and feed on only one bat species, it’s clear that they somehow find the right host.”
The scientists discovered that different bat families did have their own distinctive skin microbiome, even among samples collected from different locations. They found that differences in the skin microbiomes of certain bats does contribute to whether those bats have parasites. But not all their questions were answered.
“We weren’t able to collect the actual chemicals producing cue—secondary metabolites or volatile organic compounds—during this initial work. Without that information, we can’t definitively say that the bacteria are leading the flies to their hosts,” Lutz said.
Next Steps
“So, next steps will be to sample bats in a way that we can actually tie these compounds to the bacteria. In science, there is always a next step,” she added.
This research illustrates that there may be a reason why certain animals and humans tend to be more attractive to insects than others. It is also possible that an individual’s skin microbiome may explain why some people are more prone to mosquito and other types of insect bites.
More research and clinical studies on this topic are needed, but it could possibly lead to a clinical laboratory test to determine if an individual’s skin microbiome could contribute to his or her potential to being bitten by insects. Such a test would be quite beneficial, as insects can carry a variety of diseases that are harmful to humans.
Perhaps a precision medicine therapy could be developed to alter a person’s microbiome to make them invisible to blood-sucking insects. That would be a boon to regions of the world were diseases like malaria are spread by insect bites.
Project should provide treasure-trove of molecular information on human protein and lead to development of new biomarkers for use in clinical laboratory tests and personalized medicine
Scientists participating in the ProteomeTools project have announced the synthesis of a library of more than 330,000 peptides representing essentially all canonical proteins of the human proteome.
Translating Human Proteome into Molecular and Digital Tools
The ProteomeTools project is “a joint effort of TUM, JPT Peptide Technologies, SAP SE, and Thermo Fisher Scientific … dedicated to translating the human proteome into molecular and digital tools for drug discovery, personalized medicine, and life science research.” Over the course of the project, 1.4 million synthetic peptides covering essentially all human gene products will be synthesized and analyzed using multimodal liquid chromatography-tandem mass spectrometry (LC-MS/MS).
ProteomeTools published their first paper, “Building ProteomeTools Based on a Complete Synthetic Human Proteome,” which detailed their work in Nature Methods.
“ProteomeTools was started as a collaborative effort bringing together academic and industrial partners to make important contributions to the field of proteomics. It is gratifying to see that this work is now producing a wealth of significant results,” stated TUM researcher Bernhard Kuster, PhD, one of the leaders of the effort and senior author on the Nature Methods paper, in a TUM news release.
Thousands of New Biomarkers for Clinical Laboratories, and More!
Kuster discussed the significance of the consortium’s work in an article published in Genome Web, which described ProteomeTools as “a resource that provides the proteomics community with a set of established standards against which it can compare experimental data.”
“In proteomics today, we are doing everything by inference,” Kuster stated to Genome Web. “We have a tandem mass spectrum and we use a computer algorithm to match it to a peptide sequence that [is generated] in silico to simulate what their spectrum might look like without us actually knowing what it looks like. That is a very fundamental problem.”
Bernhard Kuster, PhD (above center), of the Technical University of Munich (TUM), led a team of researchers from the ProteomeTools project who completed a tandem mass spectrometry analysis of more than 330,000 synthetic tryptic peptides representing essentially all of the canonical human gene products. The resource eventually will cover all one million peptides. (Photo copyright: Andreas Heddergott/TUM.)
In the Genome Web article, Kuster provides an example of how researchers could use the information developed by ProteomeTools, noting it could be useful for confirming peptide identification in borderline cases. “Because the spectra for these synthetic peptides are available to everyone, you could look up a protein or peptide ID that you find exciting, but where the [experimental] data might not totally convince you as to whether it is true or not,” he explained.
Kuster also states that he believes the resource has the potential to allow “the field to move away from conventional database searching methods toward a spectral matching approach.”
The TUM news release notes that the ProteomeTools project “will generate a further one million peptides and corresponding spectra with a focus on splice variants, cancer mutations, and post-translational modifications, such as phosphorylation, acetylation, and ubiquitinylation.” The end result could be a treasure-trove of molecular information on the human proteome and development of thousands of new biomarkers for clinical use for therapeutic drugs, and more.
“Representing the human proteome by tandem mass spectra of synthetic peptides alleviates some of the current issues with protein identification and quantification. The libraries of peptides and spectra now allow us to develop new and improve upon existing hardware, software, workflows, and reagents for proteomics. Making all the data available to the public provides a wonderful opportunity to exploit this resource beyond what a single laboratory can do. We are now reaching out to the community to suggest interesting sets of peptides to make and measure as well as to create LC-MS/MS data on platforms not available to the ProteomeTools consortium,” Kuster stated in the TUM news release.
All data from the ProteomeTools project is available at the ProteomeXchange Consortium. Pathologists and clinical laboratory professionals working to develop new assays will find it to be a valuable resource.
Second-generation device is self-powered, does not require a trained operator, and amplifies the fluorescence signal by 1,000-fold, enabling early detection of cancer
Pathologists will be interested to learn that Japanese researchers have developed a second-generation lab-on-a-chip that detects microRNA (miRNA) from a tiny sample volume in only 20 minutes! Their goal is to create a point-of-care device for early detection of cancer.
This is another example of how a variety of fast-developing technologies are being brought together to create diagnostic testing systems that have capabilities that challenge the clinical laboratory analyzers used in centralized medical laboratories. (more…)
The target for this new high-speed microscope are Circulating cancer tumor cells (CTC). CTCs are the precursors to metastasis and metastatic cancer accounts for about 90% of cancer mortalities. However, CTCs are difficult to find and identify. Among a billion healthy cells, only a minute number of CTCs exist. (more…)