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Meet The OriginALS, a team of students from Ben-Gurion University who are working to end ALS

Nov 15, 2018

Ben-Gurion University of the Negev’s Life Sciences Department comprises a team of investigators conducting cutting-edge research in numerous realms of modern biology, beginning with the determination of protein structures at atom-level resolution, continuing to the examination of single-celled organisms and multi-cellular systems and reaching the study of whole animals and communities. In tackling questions related to protein science, microbiology, development, physiology, neurobiology, genomics, structural biology, ecology and other fields, Department of Life Sciences researchers rely on a wide variety of experimental systems, including bacteria, archaea, yeast, plants, insects, fish and other forms of marine life, rodents and mammals to unravel the mystery of life at the gene, protein, cell, system and organism levels.



The research efforts of department scientists are helping to provide solutions to problems related to the molecular basis of disease, cellular architecture, aging, life in extremes and wildlife conservation. At the same time, others are helping to advance aquaculture, to create enzymes capable of performing novel functions, to make biofuels and to develop an artificial visual system.



Last October a multidisciplinary team of Ben-Gurion University (BGU) undergraduate students competed in the 2018 International Genetically Engineered Competition (iGEM)  at MIT in Boston. The group presented findings on a new therapeutic approach for Amyotropic Lateral Sclerosis (ALS), known also as Lou Gehrig's disease.



The team, under the supervision of Prof. Lital Alfonta and Dr. Ramon Birnbaum of BGU’s Department of Life Sciences, competed in the Best Therapeutic Project category. More than 350 teams from 41 countries also competed in a range of categories. The OriginALS were among the teams ranked in the GOLD category.



Liat Tsoran, a member of the BGU team - aptly named The OriginALS – states that present findings will ultimately lead to a new therapeutic approach to slow down the disease, prolong survival and enhance quality-of-life for ALS patients. Currently, ALS typically claims victim's lives 2-3 years following diagnosis.



“The disease is accelerated by the dysfunction of two types of supporting cells, astrocytes and microglia," says Tsoran, who lost her father to ALS when she was a teenager. 



"Astrocytes that normally support a healthy nervous system become sick and change their shape and function, gaining a new neurotoxic activity that rapidly kills motor neurons. The microglia cells, which are part of the nervous system's immune system, over-secrete small molecules called cytokines that induce astrocytes to become reactive astrocytes," she says. 



To arrest the disease's progress, the OriginALS team use a synthetic biology system to eliminate reactive astrocytes and prolong ALS patients’ lives. This approach is based on two complementary pathways. First step is to delete the IKKB genes that are responsible for cytokine secretion in the microglia cells using a CRISPR-Cas9 genome editing system. These modified microglia cells will be unable to secrete the relevant cytokines and therefore the creation of new reactive astrocytes will be prevented.



Secondly step is to identify and specifically activate programmed cell death only in reactive astrocytes without harming healthy astrocytes, using two specific gene markers expressed only in the “sick" form of the cells. Killing toxic cells while preventing the formation of new ones will significantly reduce sick neurons, increase healthy neuron survival and slow disease progression.



“Remarkably, our therapeutic approach might open a venue for treating not only ALS, but also other neurodegenerative diseases with similar mechanisms, such as Huntington's, Alzheimer's and Parkinson's disease and brain injuries," said team member Avital Bailen, a native of Boston and third-year BGU Life Sciences student. 




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