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During the coronavirus shutdown, we are tracking online seminars and classes related to exRNA and EV research.

This blog originated as a press release from the University of Sussex. Thanks to them for allowing us to repost it here.

Scientists at the University of Sussex have identified a potential pattern within blood which signals the presence of motor neuron disease; a discovery which could significantly improve diagnosis.

Currently, it can take up to a year for a patient to be diagnosed with amyotrophic lateral sclerosis (ALS), more commonly known as motor neuron disease (MND).

But after comparing blood samples from patients with ALS, those with other motor-related neurological diseases, and healthy patients, researchers were able to identify specific biomarkers which act as a diagnostic signature for the disease.

Researchers hope that their findings, published in the journal Brain Communications, and funded by the Motor Neurone Disease Association (MNDA), could lead to the development of a blood test which will identify the unique biomarker, significantly simplifying and speeding up diagnosis.

With patients living, on average, just 2-5 years after diagnosis, this time could be crucial.

Professor Majid Hafezparast, a professor of Molecular Neuroscience at the University of Sussex, led the research in collaboration with Professors Nigel Leigh and Sarah Newbury from the Brighton and Sussex Medical School, Martin Turner from the University of Oxford, Andrea Malaspina from Queen Mary, University of London, and Albert Ludolph from the University of Ulm.

He said: “In order to effectively diagnose and treat ALS, we are in urgent need of biomarkers as a tool for early diagnosis and for monitoring the efficacy of therapeutic interventions in clinical trials.

“Biomarkers can indicate the disease is present and help us to predict its progression rate.

“In our study, we compared serum samples taken from the blood of 245 patients and controls, analysing their patterns of non-coding ribonucleic acids (ncRNA).

“We found a biomarker signature for motor neurone disease that is made up of a combination of seven ncRNAs. When these ncRNA are expressed in a particular pattern, we are able to classify whether our samples come from ALS patients or controls.”

Biomarker discovery pipeline

Dr Greig Joilin, the research fellow who undertook this work in Professor Hafezparast’s team said: “We hope that, with further work to validate these biomarkers, a blood test could be developed to help improve diagnosis of motor neuron disease.

“We are now looking to see whether they can predict prognosis to give patients and their families some insight as they begin to understand the disease. Our work could also help other scientists to measure the effectiveness of potential drug treatments against the ncRNA levels. Further, it provides new insight into the cellular and molecular events that contribute to the disease.”

ALS is a group of conditions which affects the nerves in the brain and spinal cord leading to weakness in the muscles and rapid deterioration.

Doctors still don’t know why this happens and there is currently no cure, although existing drug treatments can help patients with daily life and extend life expectancy – but only by two to four months on average.

Stephen Hawking is perhaps one of the most famous cases of motor neuron disease, but more recently Geoff Whaley and his wife Ann brought to light the troubling situation of patients in the UK who wish to end their life before the final phase of the disease takes hold.

Professor Hafezparast hopes that his team’s discovery will improve the outlook for patients by improving diagnosis and giving other researchers a valuable tool to test potential treatments. The researchers are now looking to validate this biomarker signature in a larger cohort of patients and begin to understand why these ncRNAs change in ALS patients.

Reference
Joilin G, et al. Identification of a potential non-coding RNA biomarker signature for Amyotrophic Lateral Sclerosis. (2020) Brain Commun. 2: fcaa053. doi: 110.1093/braincomms/fcaa053 PMID: 32613197.

This blog originated as a press release from ISGlobal, the Barcelona Institute for Global Health. Thanks to ISGlobal for permission to post it here.

A new study shows that extracellular vesicles from the malaria parasite Plasmodium vivax promote parasite adhesion to spleen cells

Extracellular vesicles (EVs) play a role in the pathogenesis of malaria vivax, according to a study led by researchers from the Barcelona Institute for Global Health (ISGlobal), an institution supported by the ”la Caixa” Foundation, and the Germans Trias i Pujol Research Institute (IGTP). The findings, published in Nature Communications, indicate that EVs from P. vivax patients communicate with spleen fibroblasts promoting the adhesion of parasite-infected red blood cells. These data provide important insights into the pathology of vivax malaria. The study was carried out at the Can Ruti Campus, with the participation of the IGTP Genomics platform, the Nephrology service of the Germans Trias i Pujos Hospital, and researchers from the Irsicaixa AIDS Research Institute.

Plasmodium vivax is the most widely distributed human malaria parasite, mostly outside sub-Saharan Africa, and responsible for millions of clinical cases yearly, including severe disease and death. The mechanisms by which P. vivax causes disease are not well understood. Recent evidence suggests that, similar to what has been observed with the more lethal P. falciparum, red blood cells infected by the parasite may accumulate in internal organs and that this could contribute to the pathology of the disease. In fact, the team led by Hernando A. del Portillo and Carmen Fernández-Becerra, recently showed that P. vivax-infected red blood cells adhere to human spleen fibroblasts thanks to the surface expression of certain parasite proteins, and that this expression is induced by the spleen itself. “These findings indicate that the spleen plays a dual role in malaria vivax,” says ICREA researcher Hernando A del Portillo. “On one hand, it eliminates infected red blood cells. On the other hand, it may serve as a “hiding” place for the parasite.” This could explain why P. vivax can cause severe disease in spite of low peripheral blood parasitemia.

Hernando A. del Portillo and Carmen Fernández-Becerra
Hernando A. del Portillo and Carmen Fernández-Becerra

To understand the molecular mechanisms responsible for this adhesion process, the research team turned its attention to something they have been working on for the last few years: extracellular vesicles. These small particles surrounded by a membrane are naturally released from almost any cell and play a role in communication between cells. There is increasing evidence that they could be involved in a wide range of pathologies, including parasitic diseases such as malaria. “Our new findings reveal, for what we believe is the first time, a physiological role of EVs in malaria,” says del Portillo, last author of the study.

The research team isolated EVs from the blood of patients with acute P. vivax infection or from healthy volunteers and showed a very efficient uptake of the former by human spleen fibroblasts. Furthermore, this uptake induced the expression of a molecule (ICAM-1) on the surface of the fibroblast which in turn serves as an “anchor” for the adherence of P. vivax-infected red blood cells.

“Our study provides insight into the role of extracellular vesicles in malaria vivax and supports the existence of parasite populations adhering to particular cells of the spleen, where they can multiply while not circulating in the blood” says Fernández-Becerra, senior co-author of the study. “Importantly, these hidden infections could represent an additional challenge to disease diagnosis and elimination efforts as they might be the source of asymptomatic infections,” she adds.

Reference
Toda H, Diaz-Varela M, Segui-Barber J. Plasma-derived extracellular vesicles from Plasmodium vivax patients signal spleen fibroblasts via NF-kB facilitating parasite cytoadherence. Nat Commun 11:2761. doi: 10.1038/s41467-020-16337-y PMID: 32487994.

With a focus on screening local healthcare workers and first responders, the epidemiological study seeks to understand the prevalence of coronavirus infections in the community. The lab of ERCC2’s Louise Laurent is part of the core research team.

LA JOLLA, CA—A consortium that includes many of San Diego’s top medical and scientific research institutes has launched a large-scale COVID-19 screening effort to better understand the spread and prevalence of the virus in the local community, with an initial focus on evaluating healthcare workers and first responders.

Known as the San Diego Epidemiology and Research for COVID Health (SEARCH) alliance, the cross-institutional collaboration is co-led by scientists and clinical researchers at Rady Children’s Hospital-San Diego, Rady Children’s Institute for Genomic Medicine, Scripps Research, and University of California San Diego.

As part of the SEARCH study, San Diego fire fighters are screened for SARS-CoV-2, the virus that causes COVID-19. .
Credit: Don Boomer

The research project is applying innovative technologies and screening strategies to paint a more comprehensive picture of how widely COVID-19 has spread—and continues to spread—throughout the San Diego area. All data collected will contribute to an epidemiological study that will encompass active cases of COVID-19 as well as its “silent spread” to people who never developed symptoms.

“For health officials to gain the upper hand on a virus in our community, they need more complete information about how it’s moving through the population,” says Lauge Farnaes, MD, PhD, assistant medical director at Rady Children’s Institute for Genomic Medicine. “Our goal is to fill those gaps of knowledge by leveraging San Diego’s unique expertise in science and medicine.”

As COVID-19 cases in San Diego began to rapidly increase in late March, the collaborators sprang into action. Through emails and Zoom meetings, they formulated a research proposal and created a scalable testing framework that would enable them to screen symptomatic individuals as well as people who may have COVID-19 without showing symptoms.

In the initial phase of the program, nasopharyngeal swabs are used to collect samples from study participants at a local drive-up site and the samples are screened at research laboratories at Scripps Research and UC San Diego. Any positive results are then confirmed by Rady Children’s Institute of Genomic Medicine’s nationally accredited and certified clinical laboratory.

In addition, the researchers are conducting “serosurvey” studies that look for antibodies to the virus. Serosurveys, short for serological surveys, involve finger-prick blood tests of people who haven’t been diagnosed with COVID-19 to gauge the extent to which SARS-CoV-2 has spread undetected. The program relies heavily on automation for screening, with the capacity to screen thousands of individuals daily while keeping costs low.

Since the study launched, SEARCH has enrolled more than 10,000 participants who are asymptomatic or mildly symptomatic. Thus far, researchers have found that an average of two participants per every 1,000 enrolled had a positive result for the SARS-CoV-2 virus.

Participation is voluntary but currently limited to invited healthcare workers from participating hospitals, firefighters and other first responders.

“The majority of our personnel are firefighters and lifeguards who regularly interact with the public and are at a greater risk of exposure to COVID-19. Our goal is for each and every employee to be screened,” says San Diego Fire-Rescue Chief Colin Stowell. “We appreciate the opportunity to participate in the SEARCH study, which benefits our employees and the communities we serve.”

SEARCH is also conducting large-scale SARS-CoV-2 genomic studies, analyzing changes in the virus genome from patient samples for clues to how the disease moved from city to city and person to person. All genomic data gathered by SEARCH is deidentified and then made publicly available to the scientific community to expedite discoveries that will help end the pandemic.

SEARCH’s core research team consists of the following members of the San Diego scientific and medical communities:

  • Kristian Andersen, PhD, Professor of Immunology and Microbiology at Scripps Research
  • Lauge Farnaes, MD, PhD, Assistant Medical Director at Rady Children’s Institute for Genomic Medicine
  • Rob Knight, PhD, Professor of Pediatrics, Bioengineering and Computer Science & Engineering, and Founding Director of the Center for Microbiome Innovation at UC San Diego
  • Louise Laurent, MD, PhD, Professor of Obstetrics, Gynecology, and Reproductive Sciences at UC SanDiego School of Medicine
  • Gene Yeo, PhD, MBA, Professor of Cellular and Molecular Medicine and Co-Director Bioinformatics and Systems Biology Graduate Program at UC San Diego School of Medicine

The research is made possible by a dedicated team of laboratory staff, postdoctoral researchers, graduate students, nurses, physicians, and volunteers across the partner institutions.

For more information, visit searchcovid.info.

This blog originated as a press release from Scripps Research. Thanks to Scripps and the SEARCH team for permission to post it here.