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New Resource Maps Gene-Disease Links Across Common Conditions, Paving the Way for Personalized Medicine

New Resource Maps Gene-Disease Links Across Common Conditions, Paving the Way for Personalized Medicine

17 November, 2024

A new study introduces the Proteome-Wide Association Study Hub, an innovative and powerful tool designed to explore gene-disease connections across ninety-nine common diseases. Leveraging machine learning and statistical models, the platform (PWAS Hub) identifies genes linked to specific conditions, with separate analyses for male and female subjects as well as inheritance patterns. This accessible resource is set to advance personalized medicine by providing valuable genetic insights to clinicians, researchers, and the public.

Promise in Fighting Drug-Resistant Pathogens Innovative Study Shows

Promise in Fighting Drug-Resistant Pathogens Innovative Study Shows

13 November, 2024

A new study has developed an innovative approach to combat antibiotic-resistant bacteria by tagging them with a chimeric agent that activates the immune system towards them. This approach not only enhances immune response against evasive pathogens but also shows potential for targeting a broad range of microbial threats, offering a promising new direction for fighting drug-resistant infections and advancing antimicrobial therapies

 

X-Raying Your Head Every Year at the Dentist Might Be Totally Unnecessary

X-Raying Your Head Every Year at the Dentist Might Be Totally Unnecessary

15 October, 2024

Some dentists are pushing back against the overuse of X-rays, a practice that can expose patients to unnecessary radiation and cost them extra cash.

If you’ve ever sat in a dentist’s chair, weighed down by an unwieldy, yet oddly comfortable, lead apron, wondering if your sense of time has gone completely haywire—wait, wasn’t I just here, and isn’t it too soon for more X-rays?—take comfort. You may be entirely correct.

 

Revealing the Hidden Complexity of Bacterial Biofilms

Revealing the Hidden Complexity of Bacterial Biofilms

25 September, 2024

A new perspective work reveals insights into the development of bacterial biofilms, highlighting how these communities adapt to environmental stress through complex interactions between physical and biological processes occurring in the surrounding environment. The research could have broad implications for fields such as medicine, environmental science, and industry.

 

Minimal ADHD Risk from Prenatal Cannabis Use New Study Reveals

Minimal ADHD Risk from Prenatal Cannabis Use New Study Reveals

4 September, 2024

A new study reveals nuanced findings on the neuropsychiatric risks of prenatal cannabis exposure. The research found a slight increase in the risk of ADHD and a heightened vulnerability to cannabis use in offspring. These results highlight the need for continued caution and further investigation into the long-term effects of cannabis use during pregnancy.

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A new study led by Prof. Ilan Matok and Hely Bassalov PharmD from the Department of Clinical Pharmacy at the School of Pharmacy in the Faculty of Medicine at Hebrew University in collaboration with Prof. Omer Bonne and Dr. Noa Yakirevich-Amir from the Department of Psychiatry at the Hadassah Medical Center, sheds light on the potential long-term neuropsychiatric risks associated with prenatal cannabis exposure. As the global trend toward cannabis legalization continues, the prevalence of cannabis use among pregnant women is on the rise, raising concerns about its impact on fetal development.

The study, a comprehensive systematic review and meta-analysis involving over 500,000 participants from observational studies, aimed to assess the potential risks posed by prenatal exposure to Δ9-tetrahydrocannabinol (THC), the primary psychoactive compound in cannabis. THC is known to cross the placenta, potentially affecting the developing fetal brain.

The results of the study provide a nuanced understanding of the potential risks. Most notably, the findings indicate no significant association between prenatal cannabis exposure and an increased risk of autism spectrum disorder (ASD), psychotic symptoms, anxiety, or depression in offspring. However, the study did identify a slight increase in the risk of attention-deficit/hyperactivity disorder (ADHD) and a heightened vulnerability to cannabis consumption in children exposed to cannabis in utero.

“These findings suggest that while prenatal cannabis exposure does not appear to significantly increase the risk for many neuropsychiatric disorders, there is still a mild increase in the risk for ADHD and a greater likelihood of cannabis use in the offspring,” said Prof. Matok. “This calls for cautious interpretation, as it does not confirm the safety of cannabis consumption during pregnancy.”

The study emphasizes the importance of continued research in this area, especially given that most of the studies on the subject were conducted between the 1980s and early 2000s, when cannabis was characterized by considerably lower Δ9-THC content than currently used compounds. Thus, findings presented in the current study may potentially underestimate the impact of contemporary prenatal cannabis exposure on the long-term neuropsychiatric outcomes.

“While our study provides important insights, it is crucial to recognize that these results are not definitive. Pregnant women should be aware of the potential risks, and healthcare providers should continue to advise caution when it comes to cannabis use during pregnancy,” Prof. Matok added.

This research marks a significant step forward in understanding the complex relationship between prenatal cannabis exposure and neuropsychiatric outcomes in children. As the legal landscape surrounding cannabis continues to evolve, studies like this will be essential in guiding public health recommendations and ensuring the well-being of future generations.

Methodology: The methodology of this systematic review and meta-analysis involved analyzing 18 observational studies, with 17 included in the quantitative analysis, covering 534,445 participants. The review compared neuropsychiatric outcomes in offspring exposed to cannabis prenatally to those unexposed, focusing on conditions such as ADHD, ASD, anxiety, depression, psychotic disorders, and substance use.

The studies spanned from the 1980s to early 2000s, reflecting older cannabis potencies, and included data from multiple countries, with the literature search completed by January 2024.

The research paper titled “Prenatal cannabis exposure and the risk for neuropsychiatric anomalies in the offspring: a systematic review and meta-analysis” is now available at American Journal of Obstetrics and Gynecology and can be accessed at https://www.sciencedirect.com/science/article/pii/S0002937824006823?dgcid=author#sec4 .

Researchers:

Hely Bassalov Pharm1, Noa Yakirevich-Amir2, Inbal Reuveni3, Catherine Monk4,5, Sharon Florentin2, Omer Bonne2, Ilan Matok1

Institution:

  1. Department of Clinical Pharmacy, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
  2. Department of Psychiatry, Hadassah Medical Center, Jerusalem, Israel
  3. Psychiatric Division, Sourasky Medical Center, Tel Aviv-Yafo, Israel
  4. Department of Obstetrics and Gynecology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY
  5. New York State Psychiatric Institute, New York, NY

 

The Hebrew University of Jerusalem is Israel’s premier academic and research institution. With over 23,000 students from 90 countries, it is a hub for advancing scientific knowledge and holds a significant role in Israel’s civilian scientific research output, accounting for nearly 40% of it and has registered over 11,000 patents. The university’s faculty and alumni have earned eight Nobel Prizes, two Turing Awards a Fields Medal, underscoring their contributions to ground-breaking discoveries. In the global arena, the Hebrew University ranks 81st according to the Shanghai Ranking. To learn more about the university’s academic programs, research initiatives, and achievements, visit the official website at http://new.huji.ac.il/en

 

 

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New Research Unveils Cellular Pathways to Alzheimer’s and Alternative Brain Aging

New Research Unveils Cellular Pathways to Alzheimer’s and Alternative Brain Aging

28 August, 2024

A new study has found an answer for a long-lasting question in aging research - Is Alzheimer’s disease-dementia a form of accelerated aging or is there a different path that can lead us to healthier brain aging? In an international effort, the researchers mapped 1.65 million cells from 437 aging brains, and uncovered distinct paths of cellular change in the aging brains, with one leading to Alzheimer’s disease and the other to an alternative form brain aging. They also point to  specific cell signatures predicted to advance disease once they appear in the aging brain. These findings offer new insights into the disease’s development and how it is different from healthy brain aging. As these changes in brain cells may occur many years prior to the development of symptoms and memory loss, this discovery opens the door to personalized prevention medicine that could alter disease progression and improve outcomes for individuals at risk.

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A new study, published in Nature, led by an international team, including Dr. Naomi Habib and Gilad Green from the Hebrew University of Jerusalem, Dr. Philip L. De Jager and Dr. Vilas Menon from Columbia University Irving Medical Center, Dr. David Bennett from Rush Alzheimer’s Disease Center and Dr. Hyun-Sik Yang from Harvard Medical School, has uncovered crucial insights into the cellular dynamics that contribute to brain aging and the cellular events leading to the onset and progression of Alzheimer’s disease (AD). By creating one of the biggest resources in the brain aging field, mapping over 1.65 million cells from 437 aging brains, and developing new machine learning (AI) algorithms, the research team has revealed distinct cellular paths in brain aging, providing a foundation for personalized therapeutic development targeting Alzheimer’s disease.

Mapping Brain Aging: A Closer Look at Brain Cells

This study took an in-depth approach to map the brain’s cellular environment, analyzing a unique dataset of 1.65 million single-nucleus RNA sequencing profiles from the prefrontal cortex of 437 older adults in the ROSMAP cohort at Rush University in Chicago, IL, USA. With this large dataset, researchers were able to pinpoint specific glial and neuronal cell groups linked to traits related to Alzheimer’s disease (AD). Moreover, the study zeroed in on the complex dynamics within the brain cells along the progression of aging and disease, using a new algorithm called BEYOND to model these dynamics. This approach revealed two distinct paths of brain aging, each marked by gradual coordinated changes in distinct groups of cells, which the researchers termed as “cellular communities” in the brain. Interestingly, they showed that one of these paths leads to Alzheimer’s disease, gradually leading to dementia – featured by memory loss and cognitive decline, while the other represents a healthier, non-Alzheimer’s form of brain aging. The researchers predict that these cellular changes, that start early – before any clinical signs of dementia – are actively determining the fate of the aging brain and the progression of the disease.

Important Discoveries in Alzheimer’s Disease

Alzheimer’s disease is characterized by hallmark brain pathologies, with the classical Amyloid theory of AD describing the cascade of events thought to follow the progression of the disease – starting with the accumulation of amyloid-β plaques, which then lead to accumulation of toxic neurofilament tangles, eventually leading to substantial neuronal damage and symptoms of clinical dementia. Glial cells, such as microglia and astrocytes, are supportive cells that are critical for the correct function of the brain and of neuronal cells, yet have only been recently suggested to take part in the cascade leading to Alzheimer’s disease. For example, a previous article, published in Nature Neuroscience in 2023 led by the same team with Anael Cain a PhD student in the Habib lab, laid the scientific foundation for the findings on specific cellular communities and glial cells related to Alzheimer’s disease. A key discovery from this study is the identification of specific glial cells predicted to contribute to the progression of the disease. The current study uncovered two different subsets of microglial cells, both linked to altered lipid metabolism: one was predicted by the team to drive the buildup of amyloid-β plaques, the initial hallmark pathology of Alzheimer’s disease, while the other is predicted to drive the later buildup of neurofilament tangles. The team also highlighted a group of astrocyte cells that influence directly cognitive decline, shedding more light on the complex interactions between different brain cells in the progression of Alzheimer’s disease, and highlight the key role that glial cells are taking in the progression of the disease.

Impact on Personalized Treatment Development

"The insights from this research provide a fresh understanding of how Alzheimer’s disease develops, from the very early stages, which was not possible to measure without our large dataset and unique algorithmic approach", said Dr. Habib, "by identifying the specific cells involved in each unique path of brain aging, Alzheimer’s and alternative aging, we paved the way to early identification of people at risk of Alzheimer’s disease and for creating targeted treatments for each form of brain aging to promote healthy aging". The findings lay a cellular foundation for understanding the different paths leading to Alzheimer’s. This knowledge is vital for developing personalized treatments that can act at the cellular level, potentially changing the course of the disease.

The research paper titled “Cellular communities reveal trajectories of brain aging and Alzheimer’s disease” is now available at Nature and can be accessed at https://www.nature.com/articles/s41586-024-07871-6

Nature. 2024. doi: 10.1038/s41586-024-07871-6

Researchers:

Gilad Sahar Green1, Masashi Fujita2, Hyun-Sik Yang3,4, Mariko Taga2, Anael Cain1, Cristin McCabe3, Natacha Comandante-Lou2, Charles C. White4, Anna K. Schmidtner1, Lu Zeng2, Alina Sigalov2, Yangling Wang6, Aviv Regev3,8, Hans-Ulrich Klein2, Vilas Menon2, David A. Bennett6, Naomi Habib1, Philip L. De Jager2,4

Institution:

  1. Edmond & Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem
  2. Center for Translational & Computational Neuroimmunology, Department of Neurology and Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Irving Medical Center
  3. Harvard Medical School, Boston, MA; Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women’s Hospital, Boston
  4. Broad Institute of MIT and Harvard
  5. Klarman Cell Observatory, Broad Institute of MIT and Harvard
  6. Rush Alzheimer’s Disease Center, Rush University Medical Center

 

The Hebrew University of Jerusalem is Israel’s premier academic and research institution. With over 23,000 students from 90 countries, it is a hub for advancing scientific knowledge and holds a significant role in Israel’s civilian scientific research output, accounting for nearly 40% of it and has registered over 11,000 patents. The university’s faculty and alumni have earned eight Nobel Prizes, two Turing Awards a Fields Medal, underscoring their contributions to ground-breaking discoveries. In the global arena, the Hebrew University ranks 81st according to the Shanghai Ranking. To learn more about the university’s academic programs, research initiatives, and achievements, visit the official website at http://new.huji.ac.il/en

 

 

 

 

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Identification of Novel Toxins Using Machine Learning

Identification of Novel Toxins Using Machine Learning

6 August, 2024

 

New study reveals how bacteria use a special system, like a tiny syringe, to inject toxins into other organisms. This is important because it helps us understand how bacteria interact with hosts and likely with each other. Using artificial intelligence, the researchers identified over 2,000 possible toxins, likely injected by the syringe, some of which could be potentially used as new antimicrobials. By combining AI and microbiology these findings could lead to new ways to treat infections and create new biotechnological tools.

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Microscopic Syringes and AI: Scientists Uncover New Bacterial Weapons

In a novel study, featured on the cover of August 2024 volume of Molecular Systems Biology journal, researchers have unveiled new secrets about a fascinating bacterial weapon system that acts like a microscopic syringe. Led by Dr. Asaf Levy from the Hebrew University and collaborators from the Hebrew University and from the University of Illinois Urbana-Champaine, the team has made significant strides in understanding the extracellular contractile injection system (eCIS), a unique mechanism used by bacteria and archaea to inject toxins into other organisms.

Cracking the Bacterial Code with Artificial Intelligence

The eCIS is a 100-nanometer long weapon that evolved from viruses that previously attacked microbes (phages). During evolution these viruses lost their ability to infect microbes and turned into syringes that inject toxins into different organisms, such as insects. Previously, the Levy group identified eCIS as a weapon carried by more than 1,000 microbial species. Interestingly, these microbes rarely attack humans, and the eCIS role in Nature remains mostly unknown. (Geller et al. 2021). However, we know that it loads and injects protein toxins.

The specific proteins injected by eCIS and their functions have long remained a mystery. Before the study we knew about ~20 toxins that eCIS can load and inject. To solve this biological puzzle, the research team developed an innovative machine learning tool that combines genetic and biochemical data of different genes and proteins to accurately identify these elusive toxins. The project resulted in identification of over 2,000 potential toxin proteins.

"Our discovery not only sheds light on how microbes interact with their hosts and maybe with each other, but also demonstrates the power of machine learning in uncovering new gene functions," explains Dr. Levy. "This could open up new avenues for developing antimicrobial treatments or novel biotechnological tools."

New Toxins with Enzymatic Activities against Different Molecules

Using AI technology, the researchers analyzed 950 microbial genomes and identified an impressive 2,194 potential toxins. Among these, four new toxins (named EAT14-17) were experimentally validated by demonstrating that they can inhibit growth of bacteria or yeast cells. Remarkably, one of these toxins, EAT14, was found to inhibit cell signaling in human cells, showcasing its potential impact on human health. The group showed that the new toxins likely act as enzymes that damage the target cells by targeting proteins, DNA or a molecule that is critical to energy metabolism. Moreover, the group was able to decipher the protein sequence code that allow loading of toxins into the eCIS syringe. Recently, it was demonstrated that eCIS can be used as a programmable syringe that can be engineered for injection into various cell types, including brain cells (Krietz et al. 2023). The new findings from the current paper leverage this ability by providing thousands of toxins that are naturally injected by eCIS and the code that facilitates their loading into the eCIS syringe. The code can be transferred into other proteins of interest.

From Microscopic Battles to Medical Breakthroughs

The study's findings could have far-reaching applications in medicine, agriculture, and biotechnology. The newly identified toxins might be used to develop new antibiotics or pesticides, efficient enzyme for different industries, or to engineer microbes that can target specific pathogens. This research highlights the incredible potential of combining biology with artificial intelligence to solve complex problems that could ultimately benefit human health.

"We're essentially deciphering the weapons that bacteria evolved and keep evolving to compete over resources in Nature" adds Dr. Levy.  “Microbes are creative inventors and it is fulfilling to be part of a group that discovers these amazing and surprising inventions”.

The study was led by two talented students: Aleks Danov and Inbal Pollin from the department of Plant Pathology and Microbiology, the Institute of Environmental Sciences, and was performed in collaboration with Prof. Tommy Kaplan (School of Computer Science and Engineering) and Dr. Philippos A Papathanos (Department of Entomology) from the Hebrew University of Jerusalem in collaboration with Prof. Brenda A Wilson from University of Illinois Urbana Champaign.

The research paper titled “Identification of novel toxins associated with the extracellular contractile injection system using machine learning” is now available in Molecular Systems Biology and can be accessed at https://www.embopress.org/doi/full/10.1038/s44320-024-00053-6

The cover of Molecular Systems Biology featuring eCIS injecting toxins that were predicted by AI. Artwork by Dr. Yitzhak Yadegari

Funding:

The study was funded by the Israeli Science Foundation, Israeli Ministry of Innovation, Science and Technology, Volkswagen Foundation, and a joint seed grant between the two universities.

Researchers:

Aleks Danov1, Inbal Pollin1, Eric Moon2, Mengfei Ho2, Brenda A Wilson2, Philippos A Papathanos3, Tommy Kaplan4,5 and Asaf Levy1

Institutions:

  1. Department of Plant Pathology and Microbiology, Institute of Environmental Sciences, The Robert H. Smith Faculty of Agriculture, Food & Environment, The Hebrew University of Jerusalem
  2. Department of Microbiology, University of Illinois
  3. Department of Entomology, Institute of Environmental Sciences, The Robert H. Smith Faculty of Agriculture, Food & Environment, The Hebrew University of Jerusalem
  4. School of Computer Science and Engineering, The Hebrew University of Jerusalem
  5. Department of Developmental Biology and Cancer Research, Faculty of Medicine, The Hebrew University of Jerusalem

The Hebrew University of Jerusalem is Israel’s premier academic and research institution. With over 23,000 students from 90 countries, it is a hub for advancing scientific knowledge and holds a significant role in Israel’s civilian scientific research output, accounting for nearly 40% of it and has registered over 11,000 patents. The university’s faculty and alumni have earned eight Nobel Prizes, two Turing Awards a Fields Medal, underscoring their contributions to ground-breaking discoveries. In the global arena, the Hebrew University ranks 86th according to the Shanghai Ranking. To learn more about the university’s academic programs, research initiatives, and achievements, visit the official website at http://new.huji.ac.il/en

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