A rare discovery of early rituals in the levant.
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Research
Dec 9th, 2024
TAU Discovery Decodes a Rare Neurological Disease
This breakthrough could pave the way for neurological treatments.
- Life Sciences
- Biology
Researchers at Tel Aviv University have developed an innovative research model that allowed them to decode the mechanism underlying a severe and rare neurological disease. The disease is characterized by symptoms such as epilepsy, developmental delay, and intellectual disability.
According to the researchers: "Decoding the disease mechanism is a critical step toward developing treatments targeting specific cellular functions for this disease and other conditions with similar mechanisms affecting cellular energy production".
The research was led by Tel Aviv University’s Prof. Abdussalam Azem, Dean of the Wise Faculty of Life Sciences, in collaboration with Prof. Uri Ashery and PhD student Eyal Paz from the School of Neurobiology, Biochemistry and Biophysics at the Wise Faculty of Life Sciences and the Sagol School of Neuroscience. Additional contributors included Dr. Sahil Jain and Dr. Irit Gottfried from the School of Neurobiology, Biochemistry, and Biophysics at Tel Aviv University, Dr. Orna Staretz-Chacham from the Faculty of Health Sciences at Ben-Gurion University, Dr. Muhammad Mahajnah from the Technion, and researchers from Emory University in Atlanta, USA. The findings were published in the prominent journal eLife.
TIMM50 Mutation Linked to Rare Brain Disorders
Prof. Azem explains: "The disease we studied is caused by a mutation in a protein called TIMM50, which plays a crucial role in importing other proteins into the mitochondria—the organelle considered the cell's energy powerhouse. The human mitochondria operate with about 1,500 proteins (approximately 10% of all human proteins), but only about 13 of them are produced within the mitochondria itself. The rest are imported externally through various mechanisms. In recent years, mutations in the TIMM50 protein, which is responsible for importing about 800 proteins into the mitochondria, were found to cause severe and rare neurological disease with symptoms like epilepsy, developmental delay, and intellectual disability".
Prof. Ashery adds: "Protein import into the mitochondria has been extensively studied over the years, but how a mutation in TIMM50 affects brain cells was never tested before. To investigate this for the first time, we created an innovative model using mouse neurons that mimics the disease caused by the TIMM50 protein mutation. In this study, we significantly reduced the expression of the protein in mouse brain cells and observed its impact on the cells".
How Does a Protein Defect Link Energy Loss to Epilepsy?
Eyal Paz explains: "The impairment of the protein led to two main findings: a reduction in energy production in the neurons, which could explain the developmental issues seen in the disease and an increase in the frequency of action potentials (the electrical signals that transmit information along neurons and enable communication between them). This increase in action potential frequency is known to be associated with epilepsy. The change in frequency is likely caused by significant damage to two proteins that function as potassium channels. Imbalances in potassium levels can lead to life-threatening conditions, such as arrhythmias, cardiac arrest, and muscle weakness, potentially leading to paralysis. These potassium channels may serve as potential targets for future drug treatments for the disease".
Prof. Azem concludes: "Our study decodes the mechanism of a severe and rare neurological disease caused by a mutation in a protein critical for importing proteins into the mitochondria. Understanding the mechanism is a crucial step toward treatment, as it enables the development of drugs targeting the specific issues identified. Additionally, we created a new research model based on mouse neurons that significantly advances the study of protein import into mitochondria in brain cells. We believe that our findings, combined with the innovative model, will enable more in-depth research and the development of treatments for various neurological diseases caused by similar mitochondrial dysfunction mechanisms".
Research
Dec 3rd, 2024
What Can Locusts Teach Us About Efficiency in Design?
Research shows locusts’ digging valves are built just right for their task.
- Life Sciences
Researchers at Tel Aviv University examined the mechanical wear of digging valves located at the tip of the female locust’s abdomen, used to dig pits for laying eggs 3 to 4 times during her lifetime. They found that, unlike organs with remarkably high wear resistance, such as the mandible (lower jaw), the valves wear down substantially due to intensive digging.
The researchers: “This is an instructive example of the ‘good enough’ principle in nature. Evolution saw no need to invest extra energy and resources in an organ with a specific purpose that performs its function adequately. We, humans, who often invest excessive resources in engineered systems, can learn much from nature”.
The study was led by Dr. Bat-El Pinchasik from the School of Mechanical Engineering and Prof. Amir Ayali from the School of Zoology at the Wise Faculty of Life Sciences, the Sagol School of Neuroscience and the Steinhardt Museum of Natural History at Tel Aviv University. Other participants included: PhD student Shai Sonnenreich from TAU's School of Mechanical Engineering, as well as researchers from the Technical University of Dresden in Germany, Prof. Yael Politi and a postdoc in her group, Dr. Andre Eccel Vellwock. The article was published in the prestigious journal Advanced Functional Materials.
Left to right: Prof. Amir Ayali, Dr. Bat-El Pinchasik & PhD student Shai Sonnenreich.
Dr. Pinchasik: “In my lab, we study mechanical mechanisms in nature, partly to draw inspiration for solving technological problems. Recently we collaborated with locust expert Prof. Amir Ayali in a series of studies, to understand the mechanism used by the female locust for digging a pit to lay her eggs. This unique mechanism consists of two shovel-like valves that open and close cyclically, digging into the soil while pressing the sand against the walls”.
Prof. Ayali: “We know that many mechanisms in the bodies of insects in general, and locusts in particular, are exceptionally resistant to mechanical wear. For example, the locust's mandibles, used daily for feeding, are made of a highly durable material. The digging valves, on the other hand, while subjected to substantial shear forces during digging, are used only 3 or 4 times in the female's lifetime - when she lays eggs. In this study, we sought to discover whether these digging valves, made of hard cuticular material, were also equipped by evolution with high resistance to mechanical wear”.
To address this question, the researchers examined the digging valves in three different groups of female locusts: young females that had not yet laid eggs, mature females kept in conditions that prevented them from laying eggs - to test whether age alone causes wear and adult females that had already laid eggs 3 or 4 times. To analyze the internal structure and durability of the digging valves, the researchers used several advanced technologies: confocal microscopy, 3D fluorescent imaging, and a particle accelerator (synchrotron) in collaboration with the German team. The findings indicated significant signs of wear in the valves and a lack of elements associated with high resistance to mechanical wear. Notably, no reinforcing metal ions, typical of extremely wear-resistant biological materials, were found in the valves.
Dr. Pinchasik: “A female locust's biological role is laying eggs three or four times in her life. In this study, we found that evolution has designed her digging valves to meet their task precisely—no more and no less. This is a wonderful example of the ‘good enough’ principle in nature: no extra resources are invested in an organ when they’re not needed".
“As humans, we can learn much from nature - about conserving materials, energy, and resources. As engineers who develop products, we must understand the need precisely and design an accurate response, avoiding unnecessary overengineering” - Dr. Pinchasik.
