Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Better Living through Proteomics

Published: Monday, September 09, 2013
Last Updated: Monday, September 09, 2013
Bookmark and Share
As a patient facing illness, knowing what’s ailing you can bring peace of mind and, more importantly, can inform treatment decisions.

For neglected infectious diseases, accurate diagnostic tools can be revolutionary, saving lives and shaping the health of entire communities.

One of these neglected diseases is human African trypanosomiasis (HAT). Also known as African sleeping sickness, HAT is a debilitating infection that affects thousands each year. Patients are often only diagnosed in the late stage of the disease by observing the parasites in cerebrospinal fluid, after the parasite has entered the central nervous system and caused grave illness. A low-cost, rapid “dipstick” test that could analyze a drop of patient’s blood and diagnose the illness early would make a huge impact.

Researchers have spent decades looking for proteins from the parasite itself in plasma, the liquid component of blood, with the goal of developing rapid diagnostic tests. While plasma represents an ideal source of biomarkers – a simple finger-prick is sufficient for testing – the fluid has a major flaw when it comes to diagnosis: it’s a murky soup of proteins, ranging from abundant ones such as albumin and globulins to scarcer ones such as proteins from infectious organisms.

Scientists in the Broad’s Proteomics Platform have recently developed and optimized analytic methods that, for the first time, can identify parasite proteins in the plasma of infected patients. The sophisticated approach overcomes what research scientist Rushdy Ahmad calls a “mismatch in dynamic range,” by effectively “zooming in” on the proteins they’re most interested in.

He explains that the dynamic range of proteins in plasma, meaning the lowest to highest abundance, is perhaps as great as 12 orders of magnitude. In other words, the most abundant proteins are 1 trillion times more numerous than the least abundant proteins. The dynamic range of a mass spectrometer – the gold standard for analyzing proteins – is much narrower, only 4 orders of magnitude. Running plasma through a mass spectrometer will only reveal the most abundant proteins, leaving the scarcer ones hidden below the threshold of detection.

In the new method, plasma is first “immunodepleted,” removing the top 50-70 most abundant human plasma proteins, including proteins such as albumin. “We want to collapse that dynamic range,” Ahmad explains. The technique is like skimming off the fat from soup to leave the nutritious broth, vegetables, and meat. The remaining sample is then “fractionated,” breaking it into 30 smaller samples, each containing proteins of a narrower range of abundance. “Those fractions are what we inject into the mass spectrometer,” he says. “The combination of abundant protein removal and subsequent fractionation enabled the mass spec to probe deeper into the proteome, beneath all the human proteins we’re not interested in.”

In collaboration with Terry Pearson and colleagues at the University of Victoria in British Columbia, Ahmad and platform director Steve Carr applied the new method to plasma samples from patients infected with African sleeping sickness. They were able to identify more than 250 proteins from the trypanosome parasites that underlie this dangerous disease, showing promise for the method to discover biomarkers of disease in plasma that could one day be incorporated into a diagnostic test.

More work remains before African sleeping sickness can be rapidly diagnosed in the field. The researchers must learn which of the 250 proteins make the best biomarkers to develop a diagnostic test against. In addition, the samples used in this study came from patients with late stage disease, and the team hopes to identify proteins present during early stages of infection, so they are working to get more samples from the field. They may also forge a partnership with a diagnostic company to actually create the assay.

Interestingly, the study detected more than 4000 low-abundance human proteins present in the plasma, the greatest depth of coverage of the human plasma proteome to date. Carr, Ahmad, and their colleagues are currently mining data on these thousands of proteins found in plasma to look for patterns of change during illness – signatures of host response – in diseases such as tuberculosis and malaria. Those signatures could then form the basis for new a diagnostic approach, which would use patterns of change in the levels of proteins as indicators of disease. The proteomic analysis of human plasma proteins also provides a window into disease biology and insights that could guide vaccine development.

The researchers also plan to investigate other illnesses that could benefit from improved diagnosis, such as another trypanosome illness, Chagas disease, or cancers with poor diagnostics, like lung cancer, in addition to other neglected diseases. “Now this opens up the door for all these other diseases that don’t get a lot of limelight because they’re out on the periphery,” he says. “For now, the science is progressing and this work shows the technological capability for discovery.”


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More Than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Researchers Develop a New Means of Killing Harmful Bacteria
Engineered particles are capable of producing toxins that are deadly to targeted bacteria.
Friday, June 26, 2015
Broad Institute & Google Genomics Combine Bioinformatics and Computing Expertise
Both companies explore how to break down major technical barriers that increasingly hinder biomedical research.
Thursday, June 25, 2015
CRISP-Disp Leverages CRISPR-Cas9 to Deliver RNA Structures to Targets in the Genome
A team of researchers from the Broad Institute and the Harvard Stem Cell Institute has developed CRISP-Disp, a method that expands on the CRISPR-Cas9 system, allowing researchers to display multiple, large RNA structures on the Cas9 protein.
Wednesday, June 10, 2015
GTEx: Useful Expression For Cancer Research
GTEx Project has recently published several papers reporting on findings from its two-year pilot phase.
Tuesday, May 26, 2015
Single-cell Analysis Hits its Stride
Advances in technology and computational analysis enable scale and affordability, paving the way for translational studies.
Saturday, May 23, 2015
Highly Efficient New Cas9 for In Vivo Genome Editing
New finding is expected to expand therapeutic and experimental applications of CRISPR.
Tuesday, April 07, 2015
Broad Institute of MIT and Harvard and Bayer Healthcare Expand their Partnership
Collaboration to develop therapies for cardiovascular disease.
Thursday, April 02, 2015
In vivo CRISPR-Cas9 Screen Sheds Light On Cancer Metastasis And Tumor Evolution
Genome-scale study points to drivers of tumor evolution and metastasis, provides roadmap for future in vivo Cas9 screens.
Friday, March 06, 2015
Scientists Map the Human Loop-ome, Revealing a New Form of Genetic Regulation
Researchers describe the results of a five-year effort to map, in unprecedented detail, how the 2-meter long human genome folds inside the nucleus of a cell.
Tuesday, December 23, 2014
Disorder in Gene-Control System is a Defining Characteristic of Cancer, Study Finds
Findings indicate that the disarray in the on-off mechanism is one of the defining characteristics of cancer.
Tuesday, December 23, 2014
Two Studies Identify A Detectable, Pre-Cancerous State In The Blood
Findings pave way for new lines of cancer research focused on detection and prevention.
Thursday, November 27, 2014
Dramatic Response And Resistance To Cancer Drug Traced
Sequencing reveals why thyroid tumor responded to, and eventually resisted, treatment.
Friday, October 10, 2014
Scientists Make Connection Between Genetic Variation and Immune System
Researchers demonstrate how genetic variations can influence immune cell function.
Tuesday, May 13, 2014
Taking Immune Cells for a Test Drive
Combining biological experimentation on human white blood cells with advanced computational methods can help explain the functional impact of human genetic variation on immune disease.
Monday, March 17, 2014
Charting Microbial Ecosystem of Crohn’s Disease
Study analyzed the microbiomes of 447 newly-diagnosed patients with Crohn’s and 221 healthy individuals.
Thursday, March 13, 2014
Scientific News
NIH Study Finds Calorie Restriction Lowers Some Risk Factors for Age-Related Diseases
Two-year trial did not produce expected metabolic changes, but influenced other life span markers.
Immunotherapy Agent Benefits Patients with Drug-Resistant Multiple Myeloma in First Human Trial
Daratumumab proved generally safe in patients, even at the highest doses.
Low-level Arsenic Exposure Before Birth Associated with Early Puberty in Female Mice
Study examine whether low-dose arsenic exposure could have similar health outcomes in humans.
Inciting an Immune Attack On Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
‘Mutation-Tracking’ Blood Test for Breast Cancer
Scientists have developed a blood test for breast cancer able to identify which patients will suffer a relapse after treatment, months before tumours are visible on hospital scans.
Cellular Contamination Pathway for Heavy Elements Identified
Berkeley Lab scientists find that an iron-binding protein can transport actinides into cells.
Intensity of Desert Storms May Affect Ocean Phytoplankton
MIT study finds phytoplankton are extremely sensitive to changing levels of desert dust.
Common ‘Heart Attack’ Blood Test May Predict Future Hypertension
Small rises in troponin levels may have value as markers for subclinical heart damage and high blood pressure.
LaVision BioTec Reports on the Neuro Research on the Human Brain After Trauma
Company reports on the work of Dr Ali Ertürk from the Institute for Stroke and Dementia Research at LMU Munich.
NIH Study Shows No Benefit of Omega-3 Supplements for Cognitive Decline
Research was published in the Journal of the American Medical Association.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!