A massive study of medical and genetic data shows that people with a particular version of a gene involved in immune response had a lower risk of Alzheimer’s and Parkinson’s disease.
Specific changes in our DNA that increase the risk of developing epilepsy have been discovered, in the largest genetic study of its kind for epilepsy coordinated by the International League Against Epilepsy, which includes scientists from the University of Melbourne and WEHI (Walter and Eliza Hall Institute of Medical Research).
Published today in Nature Genetics, this research advances our understanding of why epilepsy develops and could inform the development of new epilepsy treatments. The research was produced by the International League Against Epilepsy (ILAE) Consortium on Complex Epilepsies.
Epilepsy is a common brain disorder estimated to effect more than 50 million people worldwide, where nerve cell activity in the brain is disturbed, causing seizures. It has a genetic component that sometimes runs in families. In this study, researchers compared the DNA from almost 30,000 people with epilepsy to the DNA of 52,500 people without epilepsy from around the world. The differences between the two groups highlighted areas of DNA that may be involved in the development of epilepsy.
Dr. Kimathi is a medical oncologist in a community setting where she sees patients with a variety of cancer diagnoses. Recently, she had several patients with toxicities to different treatments, including tamoxifen, cisplatin, and methotrexate. Concerned, she wondered if there was a common factor these patients shared to have experienced these toxicities. On review, she found that these patients had different cancer diagnoses and did not share any known comorbidities or risk factors.
Why do some cancer patients experience toxicities from certain treatments and others don’t? Drug metabolism is highly variable among patients, and even within the same patient, depending on age and disease state. Both the toxicity and efficacy of cancer chemotherapy can be affected by many different factors, including other medications, foods, dietary supplements, environmental conditions, and genetic variants in drug-metabolizing genes and drug transporters.
Throughout Gray’s life before she got the treatment, the deformed, sickle-shaped red blood cells caused by the genetic disorder would regularly incapacitate her with intense, unpredictable attacks of pain. Those crises would send Gray rushing to the hospital for pain medication and blood transfusions. She could barely get out of bed many days; when she became a mom, she struggled to care for her four children and couldn’t finish school or keep a job.
But then she received the treatment on July 2, 2019. Doctors removed some of her bone marrow cells, genetically modified them with CRISPR and infused billions of the modified cells back into her body. The genetic modification was designed to make the cells produce fetal hemoglobin, in the hopes the cells would compensate for the defective hemoglobin that causes the disease.
A Mississippi woman’s life has been transformed by a treatment for sickle cell disease with the gene-editing technique CRISPR. All her symptoms from a disease once thought incurable have disappeared.
Continue reading “Sickle cell patient’s success with gene editing raises hopes and questions” »
Interfacing modern electronics-based technology with biology is notoriously difficult. One major stumbling block is that the way they are powered is very different. While most of our gadgets run on electrons, nature relies on the energy released when the chemical bonds of ATP are broken. Finding ways to convert between these two very different currencies of energy could be useful for a host of biotechnologies.
Genetically engineered microbes are already being used to produce various high-value chemicals and therapeutically useful proteins, and there are hopes they could soon help generate greener jet fuel, break down plastic waste, and even grow new foods in giant bioreactors. But at the minute, these processes are powered through an inefficient process of growing biomass, converting it to sugar, and feeding it to the microbes.
Now, researchers at the Max Planck Institute for Terrestrial Microbiology in Germany have devised a much more direct way to power biological processes. They have created an artificial metabolic pathway that can directly convert electricity into ATP using a cocktail of enzymes. And crucially, the process works in vitro and doesn’t rely on the native machinery of cells.
Michael Levin discusses his 2022 paper “Technological Approach to Mind Everywhere: An Experimentally-Grounded Framework for Understanding Diverse Bodies and Minds” and his 2023 paper with Joshua Bongard, “There’s Plenty of Room Right Here: Biological Systems as Evolved, Overloaded, Multi-scale Machines.” Links to papers flagged 🚩below.
Michael Levin is a scientist at Tufts University; his lab studies anatomical and behavioral decision-making at multiple scales of biological, artificial, and hybrid systems. He works at the intersection of developmental biology, artificial life, bioengineering, synthetic morphology, and cognitive science.
Continue reading “Agency, Attractors, & Observer-Dependent Computation in Biology & Beyond” »
What happens when humans begin combining biology with technology, harnessing the power to recode life itself.
What does the future of biotechnology look like? How will humans program biology to create organ farm technology and bio-robots. And what happens when companies begin investing in advanced bio-printing, artificial wombs, and cybernetic prosthetic limbs.
Continue reading “GENETIC ENGINEERING & BIOTECHNOLOGY in the Future (2077 & Beyond)” »
Several factors contribute to the development of inflamm-aging, including genetic susceptibility, visceral obesity, microbiota and gut permeability, cellular senescence, NLRP3 inflammasome activation, oxidative stress caused by mitochondrial dysfunction, immune cells dysregulation, and chronic infection (Ferrucci & Fabbri, 2018). The immune system becomes gradually dysregulated during aging, leading to elevated blood levels of pro-inflammatory mediators, such as TNFα, IL6, and C-reactive protein (Harris et al., 1999 ; Mooradian et al., 1991). Energy homeostasis also becomes dysregulated with aging, which results in the redistribution of subcutaneous fat to visceral regions and contributes to inflammation (Bouchard et al., 1993 ; Chumlea et al., 1989 ; Curtis et al., 2005). Metabolism-induced inflammation, also known as metaflammation, shares similarities with inflamm-aging, including the elevation of certain circulating pro-inflammatory cytokines (Prattichizzo et al., 2018). Therefore, the molecules that play a key role in the regulation of metabolic homeostasis potentially mediate the development of chronic inflammation during aging.
Forkhead box O1 (FOXO1) transcription factor has been indicated to be involved in the regulation of nutrient metabolism and energy homeostasis (Cheng et al., 2009 ; InSug et al., 2015 ; Matsumoto et al., 2007 ; Yang et al., 2019 ; Zhang et al., 2012). Deletion of hepatic Foxo1 improves glucose homeostasis in insulin resistant mice (Dong et al., 2008). FOXO1 inhibition by AS1842856 attenuates hepatic steatosis in diet-induced obesity mice (Ding et al., 2020). In mature macrophages, FOXO1 promotes inflammation through the activation of TLR4-and STAT6-mediated signaling pathways (Fan et al., 2010 ; Lee et al., 2022). In invertebrates, DAF-16, the Foxo homolog gene, mediates the effect of insulin/IGF signaling on lifespan (Ogg et al., 1997). Overexpression of FOXO in Drosophila and C.elegans increases their lifespan (Giannakou et al., 2004 ; Henderson & Johnson, 2001). However, studies in mammalians show that FOXO1 does not have a significant correlation with longevity (Chiba et al., 2009 ; Kleindorp et al., 2011). Considering the role of FOXO1 in regulating glucose metabolism and inflammation, we hypothesize that FOXO1 plays an important role in the regulation of aging-induced inflammation and dysregulation of glucose homeostasis.
Liver is an important metabolic organ that plays a key role in maintaining whole-body nutrient homeostasis by regulating energy metabolism, clearing xenobiotic and endobiotic, and synthesizing necessary molecules (Rui, 2014). As a result, aging-induced changes in liver contribute to systemic susceptibility to aging-related diseases. Different types of liver cells, including hepatocytes, endothelial cells, hepatic stellate cells (HSC), and macrophages, are all affected by the aging process (Hunt et al., 2019). However, most studies on liver aging focused on whole-liver tissue, which is mainly composed of parenchymal cells, hepatocytes. Thus, the effects of aging on liver nonparenchymal cells (NPCs) are less understood. In this study, we used bulk RNA-Seq and single-cell RNA (scRNA)-Seq technologies to analyze aging-induced changes, and the role of FOXO1 in aging-related processes in both whole-liver and individual liver cells, particularly liver macrophages. We found that insulin resistance, liver fat accumulation, liver inflammation, and systemic inflammation were significantly aggravated in old mice. Additionally, aging significantly increased pro-inflammatory response in Kupffer cells (KCs) and induced a functional quiescence in monocyte-derived macrophages (MDMs). FOXO1 activity was significantly enhanced in the livers of old mice and FOXO1 inhibition improved insulin resistance, hepatic steatosis, and inflammation in old mice. Furthermore, we found that FOXO1 inhibition attenuated aging-induced pro-inflammation in KCs and had a limited effect on aging-induced functional quiescence in MDMs. Taken together, this study indicates that FOXO1 plays an important role in the liver aging processes and suggests that FOXO1 is a potential therapeutic target for the treatment of aging-induced chronic diseases.
Researchers at Washington University School of Medicine in St. Louis have transformed stem cells into insulin-producing cells. They used the CRISPR gene-editing tool to correct a defect that caused a form of diabetes, and implanted the cells into mice to reverse diabetes in the animals. Shown is a microscopic image of insulin-secreting beta cells (insulin is green) that were made from stem cells produced from the skin of a patient with Wolfram syndrome.
CRISPR corrects genetic defect so cells can normalize blood sugar.
More than 20 years ago, the human genome was first sequenced. While the first version was full of “holes” representing missing DNA sequences, the genome has been gradually improved in successive rounds. Each has increased the quality of the genome and, in so doing, resolved most of the blank spaces that prevented us from having a complete reading of our genetic material.
The fundamental difficulty researchers faced in reading the genome from end to end is the enormous number of repeated sequences that populate it. The 20,000 or so genes we humans have occupy barely 2% of the entire genome. The remaining 98% is essentially made up of these families of repeated sequences, mobile elements known as transposons and retrotransposons, and—to a lesser but functionally important extent— gene expression regulatory sequences. These function as switches that determine when and where genes are turned on and off.
In March 2022, a major revision of the genome was published in the journal Science. An international consortium of researchers known as “T2T” (telomere to telomere, which are the ends of chromosomes) used a novel strategy based a type of cell (CHM13) that retains only one copy of each chromosome.
