Breaking News
April 24, 2019 - Researchers uncover potential clue to halt destruction of nerve cells in people with ALS
April 24, 2019 - Study uncovers reasons for poor mental health in bisexual people
April 24, 2019 - Screenings, interventions, and referrals can help adolescents overcome substance abuse
April 24, 2019 - Febrile seizures following vaccination are self-resolving and not dangerous
April 24, 2019 - Flow-UV inline UV-Visible spectrometer monitors dispersion in real time
April 24, 2019 - Rates of Marijuana Use in Cancer Patients on the Rise in U.S.
April 24, 2019 - Versatile drug may protect baby from hazards of intraamniotic infections
April 24, 2019 - Financial transparency may diminish trust in doctors, new study finds
April 24, 2019 - Calling all Riders: Velocity Extends Free Registration 
April 24, 2019 - The Homeless Are Dying In Record Numbers On The Streets Of L.A.
April 24, 2019 - Simple mobility test helps predict hospital readmission in elderly heart attack patients
April 24, 2019 - Novel fluorescence imaging system helps surgeons remove small ovarian tumors
April 24, 2019 - Uncovering the Structure of HIV Integrase to Inform Drug Discovery
April 24, 2019 - Medical Marijuana Use Rising Among Cancer Patients
April 24, 2019 - Artificial intelligence approach optimizes embryo selection for IVF
April 24, 2019 - Doctor or detective? Sleuthing mysteries in medical school
April 24, 2019 - CUIMC Community Gives Blood During Spring 2019 Columbia University Blood Drive
April 24, 2019 - Americans Overwhelmingly Want Federal Protections Against Surprise Medical Bills
April 24, 2019 - Making Laboratories More Efficient with the Most Modern LIMS on the Market
April 24, 2019 - Treating cancer patients with personalized, combination therapies improves outcomes
April 24, 2019 - Researchers engineer new molecules to help stop lung cancer
April 24, 2019 - Acupuncture can be a wonderful tool for preventing number of diseases
April 24, 2019 - Daily life disability before hip replacement may predict poor post-operative outcomes
April 24, 2019 - Study finds involuntary staying in housing estates to be a potential health risk
April 24, 2019 - Older kidney disease patients starting dialysis die at higher rates than previously thought
April 24, 2019 - Time-restricted eating shows promise for controlling blood glucose levels
April 24, 2019 - Ambiguous genitalia in newborns may be more common than previously thought
April 24, 2019 - Research provides important insight on the brain-body connection
April 24, 2019 - In 10 Years, Half Of Middle-Income Elders Won’t Be Able To Afford Housing, Medical Care
April 24, 2019 - Researchers study how E. coli clones have become major cause of drug-resistant infections
April 24, 2019 - Bacterial and fungal toxins found in popular electronic cigarettes
April 24, 2019 - Factors affecting absorption of ‘sunshine vitamin’ during spring/summer months
April 24, 2019 - Texting helps improve medication adherence, health outcomes for patients with schizophrenia
April 24, 2019 - Cochrane Review looks at different ways to use nicotine replacement therapies
April 24, 2019 - New review on relationship between COPD and Type 2 diabetes
April 24, 2019 - Brain areas linked to memory and emotion aid odor navigation in humans
April 24, 2019 - Brain stimulation reverses age-related memory loss
April 24, 2019 - Amid Opioid Prescriber Crackdown, Health Officials Reach Out To Pain Patients
April 24, 2019 - $4 million NIH award will help establish UCI Skin Biology Resource-based Center
April 24, 2019 - Cancer drugs reprogram genes in breast tumors to prevent endocrine resistance, finds study
April 24, 2019 - Combination-imaging technique provides new window into macaque brain connections
April 24, 2019 - Researchers identify new allergen responsible for allergy to durum wheat
April 24, 2019 - Researchers define role of rare, influential cells in the bone marrow
April 24, 2019 - DNA rearrangement may predict poor outcomes in multiple myeloma
April 24, 2019 - FDA Approves Skyrizi (risankizumab-rzaa) for Moderate to Severe Plaque Psoriasis
April 24, 2019 - Combination therapy might be beneficial in schizophrenia
April 24, 2019 - Blood test can help match cancer patients to early phase clinical trials
April 24, 2019 - Women tend to underreport snoring and underestimate its loudness
April 24, 2019 - Comprehensive molecular test introduced for diagnosis of malaria caused by P. vivax parasites
April 24, 2019 - New range prediction approach increases accuracy, safety and tolerability of proton therapy
April 24, 2019 - Need for Sedation Up for Regular Cannabis Users
April 24, 2019 - Lack of access to antibiotics is a major global health challenge
April 24, 2019 - New study provides better understanding on safety of deworming programs
April 24, 2019 - EEG used to detect impact of maternal stress on neurodevelopment in 2-month-old infants
April 24, 2019 - FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose
April 24, 2019 - A new way of finding compounds that prevent aging
April 24, 2019 - Mechanical training makes synthetic hydrogels perform more like muscle
April 24, 2019 - Study provides new insights into regulatory T cells’ role in protecting against autoimmune disease
April 24, 2019 - Pregnant women with type 1 diabetes are at greater risk of preterm birth
April 24, 2019 - ‘Tummy tuck’ can be safely performed in obese patients with no increase in complications
April 23, 2019 - ‘First’ 3-D print of heart with human tissue, vessels unveiled
April 23, 2019 - Which blood-based method works best to detect TB?
April 23, 2019 - Gene therapy cures infants suffering from ‘bubble boy’ immune disease
April 23, 2019 - Chemical-sampling wristbands detect similar exposures across three continents
April 23, 2019 - Management of Residual Limb Pain
April 23, 2019 - Molecular clock influences immune cell responses
April 23, 2019 - On the importance of culture, partnerships and diversity at the Dean’s Lecture Series
April 23, 2019 - Siddhartha Mukherjee Receives Lewis Thomas Prize for Writing About Science
April 23, 2019 - Dengue mosquito poses greatest danger of spreading Zika virus in Australia
April 23, 2019 - Scientists identify 104 high-risk genes for schizophrenia
April 23, 2019 - Abdominal etching can help patients to get classic ‘six-pack abs’ physique
April 23, 2019 - Alvogen Inc. Issues Voluntary Nationwide Recall of Fentanyl Transdermal System Due to Product Mislabeling
April 23, 2019 - Skype hypnotherapy is effective treatment for IBS
April 23, 2019 - The future hope of “flash” radiation cancer therapy
April 23, 2019 - Bicycling, Recycling, and Beyond: Public Safety to Host Shred Fest and Bike-to-Campus Day 
April 23, 2019 - Skipping breakfast linked with increased risk of death from heart disease
April 23, 2019 - Neuroscientists propose new theory about amyloid precursor protein connection in Alzheimer’s
April 23, 2019 - Mediterranean diet protects against overeating and obesity
April 23, 2019 - NUS scientists uncover novel biomarkers linked with ‘chemobrain’
April 23, 2019 - Novel ECCITE-seq technique expands multimodal single cell analysis
Salk research in yeast leads to serendipitous finding about hypomyelinating leukodystrophy

Salk research in yeast leads to serendipitous finding about hypomyelinating leukodystrophy

image_pdfDownload PDFimage_print

Studying the fundamental aspects of biology can sometimes lead to unexpected findings that directly relate to human disease. In one of the latest examples of scientific serendipity, researchers from the Salk Institute found that an important quality control mechanism in baker’s yeast is closely connected to hypomyelinating leukodystrophy, a debilitating disease found in children.

The findings, reported September 7, 2018, in the journal eLife, could indicate a therapeutic approach for this rare disease, as well as for multiple sclerosis and other neurodegenerative diseases.

“It’s a total coincidence that we made this discovery,” says Salk American Cancer Society Professor Tony Hunter, the paper’s senior author. “We wouldn’t have guessed that this yeast protein would play a role in human disease in this way.”

In the face of genetic damage–from cancer or other diseases–cells mobilize molecular processes that act as repair crews. For the past decade or so, one focus of Hunter’s lab has been the study of certain proteins that regulate these repair procedures through a process called sumoylation. SUMO addition to proteins, or sumoylation, acts as a quality-control mechanism to signal to a cell that the protein should be cleared out.

In the current study, Salk Research Associate Zheng Wang, the paper’s first author, set up a genetic screening test in yeast to determine which proteins relied on sumoylation to function properly. He identified several subunits of a protein complex called RNA polymerase III–which plays an important role in copying DNA into RNA–among those that were affected. The team found that when Pol III was mutated the cells stop growing, because the mutant Pol III cannot make enough transfer RNAs (small RNAs that are needed for cells to synthesize proteins). However, that defect could be rescued by reducing sumoylation in the yeast cells.

At the same time the research with Pol III was going on Hunter’s lab, other groups studying hypomyelinating leukodystrophy–a neurodegenerative disease characterized by the loss of the protective insulation around nerve cells (myelin)–discovered that the condition was caused by mutations in Pol III. Although Pol III was known to be important for the regulation of cell growth, this was the first time a specific disease had been connected with defects in Pol III.

Due to the loss of myelin insulation around nerves, people with hypomyelinating leukodystrophy have delayed development, intellectual disabilities and impaired movement. There is currently no therapy available. However, the Hunter lab’s new findings suggest that one way to limit the effects of these mutations may be to partially inhibit sumoylation, which would in turn block the effects of the mutated Pol III.

The research still has a long way to go: sumoylation is important for many other functions as well, so inhibiting it in all cells would not be a useful approach. Furthermore, although the new findings partially explain the loss of myelin due to genetic mutation, the investigators still don’t know why these Pol III mutations affect oligodendrocytes–the cells that coat the nerve axons with myelin–in particular.

Hunter’s lab is now working in a collaboration studying mouse models that have mutated Pol III to investigate the effect of these mutations on embryonic development. His group also plans to study similar Pol III mutations in induced pluripotent stem cells (iPSCs) as well as in other types of cells, including cancer cells, to try to gain further insight into the mechanisms that underlie Pol III defects.

Tagged with:

About author

Related Articles