Potential Lung Disease Treatment – Amoeba Biology Reveals COPD Therapy Strategy
Amoebas are single-celled organisms that have pseudopodia (podlike appendages) that help in the movement and ingestion. Scientists at John Hopkins Medicine have experimented on this peculiar organism that has revealed a genetic pathway activating which the mucus resulting from chronic obstructive pulmonary disease can be cleared out from affected patients’ lungs.
Johns Hopkins University School of Medicine’s Professor of oncology, pharmacology and molecular sciences, medicine (pulmonary division), cell biology, biomedical and chemical engineering, Doug Robinson (Ph.D.), explained how the experiments took place with the collaboration of fundamental biologists and physician-scientists to comprehend major human diseases that are core biology-related.
COPD (Chronic obstructive pulmonary disease) affects more than 15M US adults and is the 4th biggest death-causing disease in the country as per reports by the U.S. Centers for Disease Control and Prevention. People with this disease have lungs that fill up with phlegm and mucus and symptoms like wheezing, chronic cough, difficulty in breathing. Despite research spanning decades, no effective cure or treatment is available for COPD, which mainly (3/4th of cases) manifests due to smoking cigarettes.
The study that reveals the potential lung disease treatment was published in The Journal of Science on February 25th, 2021. It reports the scientists’ focus on an organism as simple as an amoeba to identify protective genes against damage caused by smoking.
Ramana Sidhaye (M.D.), John Hopkins University’s Professor of medicine in the Pulmonology Division, collaborated with Robinson and Corrine Kliment (M.D., Ph.D.), former lab member. The 3 researchers took into account the retaining of genetic pathways across the animal kingdom as species evolved.
Meanwhile, Dictyostelium discoideum (a soil-dwelling amoeba) was considered owing to the number of studies that have revealed secrets of its communication and cell movement abilities. Lab-grade cigarette smoke was infused into the nutrient broth containing amoeba via a tube, and then the organism was engineered for the sake of detecting smoke-protectant genes.
The study that reveals a potential lung disease treatment showed that certain “survivor” cells had the most prominent protective genes – ANT (Adenine Nucleotide Translocase). The proteins synthesized from this group of genes are present in the mitochondria, cell surface, and cell membrane. Highly active ANT genes cause greater mitochondrial functioning, which confers enough energy required for protection. The team suspects tp have also aided the organism in mastering the damaging effects of cigarette smoke.
To study these resilient genes’ behavior in humans, tissue samples from the lung lining 28 COPD patients were taken. The samples from these patients (treated at the University of Pittsburgh) were analyzed against 20 normal lung tissue samples. Approximately 20% lesser ANT2 gene expression was found in COPD patients. The researchers also discovered the loss of ANT2 expression in smoke-exposed mice.
The study’s next step was to discover the protection mechanism conferred by the ANT2 gene against the chemicals from cigarette smoke. They discovered that cilia (fingerlike projections) in the lung cell-lining helped remove particles and mucus from the lungs. Humans and other mammals with the ANT2 gene have enhanced regular sweeping ability in their cilia due to the watery substance released in and around the cilia localized by the ANT2 proteins.
Studying the potential lung disease treatment, Robinson said that COPD patients’ lungs have thicker mucus that is difficult for the cilia to remove. Added to this, ANT2-lacking human lungs exposed to smoke had cilia with 35% reduced capacity to sweep out the mucus, compared to individuals with normal ANT2 functioning. Lower beating-out rates were contributed by the increased density of the watery liquid close to the ciliated cells, which was identified by its reduced height in the lungs.
To overcome this, the lung cells were engineered to contain overly active ANT2 genes. Upon exposing these cells to smoke, it was revealed that cilia beating was comparable to normal lung cells (not exposed to smoke). Additionally, the watery liquid was 2.5 times higher in levels than that seen in ANT2-lacking cells.
Robinson explained how cells’ ability to repurpose ANT genes results in better hydration layer in the lung airways. He marveled at the ability of mitochondrial genes to help in cilia functioning. The study revealed that a potential lung disease treatment could be formulated by gene therapy approaches involving the addition of ANT2 gene function into the cells in the lungs’ lining.
