Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Breaking the code

22.11.2013
You may be sensitive to gluten, but you're not sure. Perhaps you can't put your finger on a recurring malaise, and your doctor is at a loss to figure it out.

A diagnostic method recently developed by UC Santa Barbara professor Patrick Daugherty can reveal — on a molecular level — the factors behind conditions thought to have environmental triggers.


By cross-referencing the amino acid sequence of peptides strongly associated with illnesses with a library of known peptides, researchers may be able to map antigens with identical sequences to their environment, thus uncovering and confirming environmental triggers for diseases such as Type 1 diabetes, schizophrenia, and autism.

Credit: Peter Allen

By decoding an individual's immune system, this elegant and accurate method can demystify, diagnose and provide further insight into conditions like celiac disease, multiple sclerosis, preeclampsia and schizophrenia.

"We have two goals," said Daugherty, a researcher with the Department of Chemical Engineering at UCSB and the campus's Center for BioEngineering. "We want to identify diagnostic tests for diseases where there are no blood diagnostics … and we want to figure out what might have given rise to these diseases."

The process works by mining an individual's immunological memory — a veritable catalog of the pathogens and antigens encountered by his or her immune system.

"Every time you encounter a pathogen, you mount an immune response," said Daugherty. The response comes in the form of antibodies that are specific to the antigens — molecular, microbial, chemical — your body is resisting, and the formation of "memory cells" that are activated by subsequent encounters with the antigen. Responses can vary, from minor reactions — a cough, or a sneeze — to serious autoimmune diseases in which the body turns against its own tissues and its immune system responds by destroying them, such as in the case of Type 1 diabetes and celiac disease.

"The trick is to determine which antibodies are linked to specific diseases," said Daugherty. Celiac disease sufferers, for example, will have certain antibodies in their blood that bind to specific peptides — short chains of amino acids — present in wheat, barley and rye. These peptides are the gluten that is the root of allergies and sensitivities in some people. Like a lock and key, these antibodies — the locks — bind only to certain sequences of amino acids that comprise the peptides — the keys.

"People with celiac disease have two particular antibody types in their blood, which have proved to be enormously useful for diagnosis," said Daugherty.

However, sheer variety and number of antibodies present in a person's blood at any given time has been a challenge for researchers trying to link specific illnesses with specific antibody molecules. One antigen can stimulate the production of many antibodies in response. What's more, each individual's antibodies to even the same antigen differ slightly in their form. The idea of using molecular separation to find the disease antibodies has been around for over 20 years, said Daugherty, but no one had figured quite how to sift through the vast amount of molecules.

To sort through perhaps tens of thousands of antibody molecules present in a person's blood, the research team, including postdoctoral researcher John T. Ballew from UCSB's Biomolecular Science and Engineering graduate program, mixes a sample of a subject's blood — which contains the antibody molecules — with a vast number of different peptides (about 10 billion).

"All the keys associate with their preferred lock," said Daugherty. "The peptides that can bind to an antibody, do so." The researchers then pull out the disease-bound pairs, in a process that progressively decreases the number of antibodies-peptide pairs that are most unique to a particular disease. Repeated with subsequent patients who may have the same symptoms, phenotypes or genetic dispositions, continues to whittle down the size of the peptide pool. Further in vitro evolution of the best draft peptides can identify the particular sequence of amino acid keys that fit into the antibody locks. This sequence can be used to confirm the antibodies in question as the biomarkers specifically associated with the disease.

"The diagnostic performance of the reagents generated with this approach is excellent," said Daugherty. "We can discover biomarkers with as little as a drop of blood, and the peptides discovered can be adapted into preferred low cost testing platforms widely used in clinical practice."

The amino acid sequence of the evolved peptides, when cross-referenced with a database of known proteins, can identify the antigens (that contain the same peptide sequence). This, in turn, can then yield clues into what factors in the patient's environment may have contributed to the disease. The process may be used to gain insight on diseases that are thought to have environmental triggers, including Type-1 diabetes, autism, schizophrenia/bipolar disorder, Crohn's disease, Parkinson's disease, and perhaps even Alzheimers disease. In cases, such as Graves' disease, where an antibody is identified as the cause (as opposed to simply an indicator) knowing the antibody's structure can lead to more effective therapies.

"If you can get rid of the antibody, you can treat the disease," said Daugherty. "By finding these keys, you can block the antibody."

Research on this study was performed also by partners from the Mayo Clinic; the University of Tampere in Finland; UC San Diego; and Seinäjoki Central Hospital in Finland. Their findings are published in a paper titled "Antibody biomarker discovery through in vitro directed evolution of consensus recognition epitopes," in the Nov. 11 online issue of the Proceedings of the National Academy of the Sciences.

Sonia Fernandez | EurekAlert!
Further information:
http://www.ucsb.edu

More articles from Health and Medicine:

nachricht Team discovers how bacteria exploit a chink in the body's armor
20.01.2017 | University of Illinois at Urbana-Champaign

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>