Lifeboat Foundation

Over the recent decades, comprehensive genome-wide association studies (GWAS) have indicated the potential influence of genetic factors on one’s alcohol consumption volume and identified over 100 related variants^6,7. However, a predominant proportion of the identified variants are localized within noncoding regions, and their effect sizes tend to be small, making interpretation and identification of the causal gene challenging⁸. In addition, previous GWAS mainly utilized imputed genotype data, which only cover limited regions of the genome, and thus may have missed many potential genes. Furthermore, GWAS studies focused mainly on common variants, and few studies have investigated rare variants associated with alcohol consumption, which yield greater potential to interpret biological function and elucidate mechanisms⁹. Although there are studies that have attempted to leverage exome chip data to identify rare variants contributing to alcohol consumption, the sample size was small and limited regions of the whole exome were examined¹⁰.

The introduction of whole exome sequencing (WES) provides a great chance to overcome the limitations of previous genetic studies on alcohol consumption with a substantially larger amount of rare and ultra-rare protein-coding variants^11,12,13. Collapsing of loss-of-function (LOF) variants helps estimate the effect direction of associated genes^13,14. When combined with large-scale population cohorts with multi-modal phenotypic data, WES would greatly facilitate our understanding of the genetic underpinnings of alcohol consumption as well as its implication on physical and mental health⁶. However, to our knowledge, there have been few large-scale WES studies on alcohol consumption, let alone elucidating the potential implications of the identified genes^10,15. Meanwhile, as indicated by a previous genome-wide association study, significant genetic associations existed between alcohol consumption and several body health phenotypes⁷. The application of phenome-wide analysis for alcohol-related genes can help extend and deepen our current comprehension of the association between alcohol consumption and human health.

Hence, aiming to refine the genetic architecture of alcohol consumption, we conduct an exome-wide association study (ExWAS) for alcohol consumption among 304,119 individuals from the UK Biobank (UKB). We also examine the rare-variant associations with genes reported by previous GWAS^6,7,16,17. Finally, we provide biological insights into the identified genes via bioinformatics analyses and phenome-wide association analysis (PheWAS).

Genome editing stands as one of the most transformative scientific breakthroughs of our time. It allows us to dive into the very code of life and make precise modifications. Imagine being able to rewrite the genetic instructions that determine almost everything about an organism—how it looks, behaves, interacts with its environment, and its unique characteristics. This is the power of genome editing.

We use genome editing tools to tweak the genetic sequences of microbes, animals, and plants. Our goal? To develop desired traits and eliminate unwanted ones. This technology’s impact has been felt across biotechnology, human therapeutics, and agriculture, bringing rapid advancements and solutions.

The most widely used proteins in genome editing are Cas9 and Cas12a. These proteins are like the scissors of the genetic world, allowing us to cut and edit DNA. However, they are quite bulky, consisting of 1,000–1,350 amino acids. Advanced editing technologies like base editing and prime editing require the fusion of additional proteins with Cas9 and Cas12a, making them even bulkier. This bulkiness poses a challenge to delivering these proteins efficiently into cells, where the genetic material resides.

Lecture by Dr Jack Szostak, 2009 Nobel laureate in Physiology or Medicine, at the Molecular Frontiers Symposium \.

Scientists at Weill Cornell Medicine discovered a previously unknown link between two key pathways that regulate the immune system in mammals — a finding that impacts our understanding of chronic inflammatory bowel diseases (IBD). This family of disorders severely impacts the health and quality of life of more than 2 million people in the United States.

The immune system has many pathways to protect the body from infection, but sometimes an overactive immune response results in autoimmune diseases including IBD, psoriasis, rheumatoid arthritis and multiple sclerosis. Interleukin-23 (IL-23) is one such immune factor that fights infections but is also implicated in many of these inflammatory diseases. However, it was unknown why IL-23 is sometimes beneficial, and other times becomes a driver of chronic disease.

In the study, published June 12 in Nature, the team found that IL-23 acts on group 3 innate lymphoid cells (ILC3s), a family of immune cells that are a first line of defense in mucosal tissues such as the intestines and lungs. In response, ILC3s increase activity of CTLA-4, a key regulatory factor that prevents the immune system from attacking the body and beneficial gut microbiota. This interaction critically balances the pro-inflammatory effects IL-23 to maintain gut health, but is impaired in IBD.

Is Medical Director of the Adult Extracorporeal Membrane Oxygenation (ECMO) Program at Methodist Hospital, San Antonio, Texas. He is also the Medical Director of the Cardiovascular Intensive Care Unit at Methodist Healthcare System and the Texas IPS Critical Care Service Line (https://texasips.com/jeffrey-dellavol…). He also serves as chair of the Joint Society of Critical Care Medicine/Extracorporeal Life Support Organization Task Force and has created a platform for ECMO training and ECMO transport (https://ecmotransports.com/about/).

ECMO is a form of extracorporeal life support, providing prolonged cardiac and respiratory support to persons whose heart and lungs are unable to provide an adequate amount of oxygen, gas exchange or blood supply (perfusion) to sustain life.

Continue reading “Dr. Jeffrey DellaVolpe, MD — Saving Lives With Extracorporeal Membrane Oxygenation (ECMO) Technology” »

Common treatments for Parkinson’s disease can address short-term symptoms, but can also cause extensive problems for patients in the long run. Namely, treatments can cause dyskinesia, a form of uncontrollable movements and postures.

In a recent study published in The Journal of Neuroscience, researchers at the University of Alabama at Birmingham took a different approach to dyskinesia and treated it like a “bad motor memory.” They found that blocking a protein called Activin A could halt dyskinesia symptoms and effectively erase the brain’s “bad memory” response to certain Parkinson’s treatments.

“Instead of looking for a completely alternative treatment, we wanted to see if there was a way to prevent dyskinesia from developing in the first place,” said David Figge, M.D., Ph.D., lead study author and assistant professor in the UAB Department of Pathology. “If dyskinesia does not occur, then patients could potentially stay on their Parkinson’s treatment for longer.”

Eexxeccellent.

Human brains outperform computers in many forms of processing and are far more energy efficient. What if we could harness their power in a new form of biological computing?

Continue reading “Thomas Hartung and colleagues | The future of organoid intelligence | Frontiers Forum Deep Dive 2023” »

In multicellular organisms, many biological pathways exhibit a curious structure, involving sets of protein variants that bind or interact with one another in a many-to-many fashion. What functions do these seemingly complicated architectures provide? And can similar architectures be useful in synthetic biology? Here, Dr. Elowitz discusses recent work in his lab that shows how many-to-many circuits can function as versatile computational devices, explore the roles these computations play in natural biological contexts, and show how many-to-many architectures can be used to design synthetic multicellular behaviors.

About Michael Elowitz.
Michael Elowitz is a Howard Hughes Medical Institute Investigator and Roscoe Gilkey Dickinson Professor of Biology and Biological Engineering at Caltech. Dr. Elowitz’s laboratory has introduced synthetic biology approaches to build and understand genetic circuits in living cells and tissues. As a graduate student with Stanislas Leibler, Elowitz developed the Repressilator, an artificial genetic clock that generates gene expression oscillations in individual E. coli cells. Since then, his lab has continued to design and build synthetic genetic circuits, bringing a “build to understand” approach to bacteria, yeast, and mammalian cells. He and his group have shown that gene expression is intrinsically stochastic, or ‘noisy’, and revealed how noise functions to enable probabilistic differentiation, time-based regulation, and other functions. Currently, Elowitz’s lab is bringing synthetic approaches to understand and program multicellular functions including multistability, cell-cell communication, epigenetic memory, and cell fate control, and to provide foundations for using biological circuits as therapeutic devices. His lab also co-develops systems such as “MEMOIR” that allows cells to record their own lineage histories and tools for RNA export, and precise gene expression. Elowitz received his PhD in Physics from Princeton University and did postdoctoral research at Rockefeller University. Honors include the HFSP Nakasone Award, MacArthur Fellowship, Presidential Early Career Award, Allen Distinguished Investigator Award, the American Academy of Arts and Sciences, and election to the National Academy of Sciences.

Continue reading “Many-to-Many Networks: Multifunctional Modules for Multicellularity — Michael Elowitz” »

Summary: Researchers have discovered how glial cells can be reprogrammed into neurons through epigenetic modifications, offering hope for treating neurological disorders. This reprogramming involves complex molecular mechanisms, including the transcription factor Neurogenin2 and the newly identified protein YingYang1, which opens chromatin for reprogramming.

The study reveals how coordinated epigenome changes drive this process, potentially leading to new therapies for brain injury and neurodegenerative diseases.