Genetic Engineering: Changing the Number of Chromosomes in Plants Using Molecular Scissors

For the first time, KIT researchers managed to reduce the number of chromosomes in a plant by fusing two chromosomes.
Illustration Credit: Michelle Rönspies – KIT

Higher yields, greater resilience to climatic changes or diseases – the demands on crop plants are constantly growing. To address these challenges, researchers at Karlsruhe Institute of Technology (KIT) are developing new methods in genetic engineering. In cooperation with other German and Czech researchers, they succeeded for the first time in leveraging the CRISPR/Cas molecular scissors for changing the number of chromosomes in the Arabidopsis thaliana model organism in a targeted way – without any adverse effects on plant growth. This discovery opens up new perspectives for plant breeding and agriculture.  

The world’s oldest RNA extracted from woolly mammoth

“Such studies could fundamentally reshape our understanding of extinct megafauna as well as other species, revealing the many hidden layers of biology that have remained frozen in time until now”, says postdoc at the University of Caopenhagen, Emilio Mármol.
Image Credit: Scientific Frontline / stock image

Scientists have taken an important step closer to understanding the mythical mammoths that roamed the Earth thousands of years ago. 

For the first time ever, a research team has succeeded in isolating and sequencing RNA molecules from woolly mammoths dating back to the Ice Age. These RNA sequences are the oldest ever recovered and come from mammoth tissue preserved in the Siberian permafrost for nearly 40,000 years. The study, published in the journal Cell, shows that not only DNA and proteins, but also RNA, can be preserved for very long periods of time, and provide new insights into the biology of species that have long since become extinct. 

Oxford scientists capture genome’s structure in unprecedented detail

Detailed map of the genome one pixel per nucleotide
Image Credit: Radcliffe Department of Medicine

Scientists from Oxford's Radcliffe Department of Medicine have achieved the most detailed view yet of how DNA folds and functions inside living cells, revealing the physical structures that control when and how genes are switched on.

Using a new technique called MCC ultra, the team mapped the human genome down to a single base pair, unlocking how genes are controlled, or, how the body decides which genes to turn on or off at the right time, in the right cells. This breakthrough gives scientists a powerful new way to understand how genetic differences lead to disease and opens up fresh routes for drug discovery.

‘For the first time, we can see how the genome’s control switches are physically arranged inside cells, said Professor James Davies, lead author of the study.

‘This changes our understanding of how genes work and how things go wrong in disease. We can now see how changes in the intricate structure of DNA leads to conditions like heart disease, autoimmune disorders and cancer.’

New Genetic Cause of Microcephaly Identified

Huu Phuc Nguyen, Pauline Ulmke, and Tran Tuoc (from left) contributed significantly to the work. 
Photo Credit: © RUB, Marquard

Microcephaly is a congenital malformation that leads to a significantly reduced brain size and is often accompanied by developmental delay. An international research team led by Dr. Tran Tuoc from the Department of Human Genetics at Ruhr University Bochum, Germany, has discovered a previously unknown genetic cause for this condition. Mutations in the EXOSC10 gene – a central component of the RNA degradation complex (“exosome”) – cause primary microcephaly. The work was published in the journal BRAIN. 

Precise balance of stem cells

During human brain development, neural stem cells must balance self-renewal and differentiation to build the cerebral cortex – the brain’s outer layer responsible for cognition and perception. If this balance is disturbed, malformations occur. “Recent advances in genome sequencing and genetic engineering are transforming our understanding of neurodevelopmental disorders”, Tuoc Tran says.

Did Lead Limit Brain and Language Development in Neanderthals and Other Extinct Hominids?

UC San Diego researchers have found high levels of lead in the teeth of both Neanderthals (left) and modern humans (right). However, a gene mutation may have protected modern human brains, allowing language to flourish.
Photo Credit: Kyle Dykes/UC San Diego Health Sciences

Ancient human relatives were exposed to lead up to two million years ago, according to a new study. However, a gene mutation may have protected modern human brains, allowing language to flourish.

What set the modern human brain apart from our now extinct relatives like Neanderthals? A new study by University of California San Diego School of Medicine and an international team of researchers reveals that ancient hominids — including early humans and great apes — were exposed to lead earlier than previously thought, up to two million years before modern humans began mining the metal. This exposure may have shaped the evolution of hominid brains, limiting language and social development in all but modern humans due to a protective genetic variant that only we carry. The study was published in Science Advances.

The researchers analyzed fossilized teeth from 51 hominids across Africa, Asia and Europe, including modern and archaic humans such as Neanderthals, ancient human ancestors like Australopithecus africanus, and extinct great apes such as Gigantopithecus blacki.

Researchers uncover possible new treatment to target a devastating childhood brain cancer

Professor Peter Lewis
Photo Credit: Courtesy of University of Wisconsin–Madison

Using fruit flies, University of Wisconsin–Madison researchers have developed a new model for investigating the genetic drivers of a rare but aggressive brain tumor in children. The work has already identified potential treatment targets for the deadly cancer that has previously had few therapeutic options.

“Right now, these tumors are incurable, and the standard of care hasn’t changed for 30 years,” says Peter Lewis, a professor in the Department of Biomolecular Chemistry.

The cancer is called pediatric diffuse midline glioma. As its name suggests, the malignancy arises along the midline of the brain or spinal cord and infiltrates surrounding tissue in a way that makes it impossible to remove with surgery. Instead, typical treatment revolves around radiation therapy, and that extends a patient’s life by just months or at most a few years.

Professor Peter Lewis: “What we found might extend well beyond these very rare childhood tumors into more common ones.”

The limited treatment options have driven researchers to more closely examine the genetic mutations that cause the cancer to develop in the first place, with an eye on finding ways to disrupt that process. 

In the case of diffuse midline glioma, previous research identified mutations in certain DNA-packaging proteins as a likely culprit.

Deciphering the mechanisms of genome size evolution

The sequencing of the genomes of a spider from the mainland (Dysdera catalonica, left) and one from the Canary Islands (Dysdera tilosensis, left) opens a new perspective for understanding how genome size evolves in similar species, an enigma that has baffled the scientific community for years.
Photo Credit: Courtesy of University of Barcelona

This study contradicts the more traditional evolutionary view — on island-colonizing species, whose genomes are larger and often have more repetitive elements — and expands the scientific debate on a major puzzle in evolutionary biology: how and why does genome size change during the evolution of living beings?

The study is led by Julio Rozas and Sara Guirao, experts from the Faculty of Biology and the Biodiversity Research Institute (IRBio) of the University of Barcelona. The paper, whose first author is Vadim Pisarenco (UB-IRBio), also involves teams from the University of La Laguna, the Spanish National Research Council (CSIC) and the University of Neuchâtel (Switzerland).

This research offers a surprising perspective to explain a phenomenon that has puzzled scientists for decades: the size of the genome — the total number of DNA base pairs encoding an organism’s genetic information — varies enormously between species, even those with similar biological complexity.

Study reveals genetic link between childhood brain disorder and Parkinson's disease in adults

Image Credit: Dmitriy Kievskiy

Errors in a gene known to cause a serious neurodevelopmental condition in infants are also linked to the development of Parkinson’s disease in adolescence and adulthood, according to new research

The study, published in the Annals of Neurology, looked at a gene called EPG5. Errors in this gene are already known to cause Vici syndrome – a rare and severe inherited neurodevelopmental condition that presents early in life and affects multiple organ systems. Now researchers at King’s College London, University College London (UCL), the University of Cologne and the Max Planck Institute for Biology of Ageing have found that errors in the same gene are linked to changes in nerve cells that lead to more common age-related conditions like Parkinson’s disease and dementia.

Cholesterol-lowering drugs could reduce the risk of dementia

Low cholesterol can reduce the risk of dementia, a new University of Bristol-led study with more than a million participants has shown.

The research, led by Dr Liv Tybjærg Nordestgaard while at the University of Bristol and the Department of Clinical Biochemistry at Copenhagen University Hospital – Herlev and Gentofte, found that people with certain genetic variants that naturally lower cholesterol have a lower risk of developing dementia.

The study, which is based on data from over a million people in Denmark, England, and Finland, has been published in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 

Some people are born with genetic variants that naturally affect the same proteins targeted by cholesterol-lowering drugs, such as statins and ezetimibe. To test the effect of cholesterol-lowering medication on the risk of dementia, the researchers used a method called Mendelian Randomization — this genetic analysis technique allowed them to mimic the effects of these drugs to investigate how they influence the risk of dementia, while minimizing the influence of confounding factors like weight, diet, and other lifestyle habits.

Researchers discover of a new type of diabetes in babies

Photo Credit: Rene Terp

Advanced DNA sequencing technologies and a new model of stem cell research has enabled an international team to discover a new type of diabetes in babies.

The University of Exeter Medical School worked with Université Libre de Bruxelles (ULB) in Belgium and other partners to establish that mutations in the TMEM167A gene are responsible for a rare form of neonatal diabetes.

Some babies develop diabetes before the age of six months. In over 85 per cent of cases this is due to genetic mutation in their DNA. Research led by the University of Exeter found that in six children with additional neurological disorders such as epilepsy and microcephaly identified alterations in a single gene: TMEM167A.

To understand its role, ULB researcher Professor Miriam Cnop’s team used stem cells differentiated into pancreatic beta cells and gene-editing techniques (CRISPR). They found that when the TMEM167A gene is altered, insulin-producing cells can no longer fulfill their role. They then activate stress mechanisms that lead to their death.

Breast Cancer Polygenic Risk Score Associated with Outcomes after In Situ Breast Disease

Photo Credit: National Cancer Institute

Studying a person’s genetic makeup can predict if they will go on to develop invasive breast cancer after abnormal cells have been found in their breast tissue.

For the first time, researchers at King’s College London have shown the connection between a person’s genetic risk score and their risk of developing the disease after irregular cells have been detected.

The research, published in Cancer Epidemiology, Biomarkers & Prevention and funded by Breast Cancer Now, included over 2,000 women in the UK who had been tested for 313 genetic changes, known as a genetic risk score.

These patients had already been diagnosed with either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) – the most common types of abnormal cells found in breast tissue.

A genetic risk score estimates a person's inherited likelihood of developing a disease or trait by combining the influence of multiple common genetic variants.

Hidden genetic risk could delay diabetes diagnosis for Black and Asian men

 

Photo Credit: Barbara Olsen

A common but often undiagnosed genetic condition may be causing delays in type 2 diabetes diagnoses and increasing the risk of serious complications for thousands of Black and South Asian men in the UK – and potentially millions worldwide.

The new study is conducted by the University of Exeter, in collaboration with Queen Mary University of London (QMUL) and funded through a Wellcome Discovery Award. It has found around one in seven Black and one in 63 South Asian men in the UK carry a genetic variant known as G6PD deficiency. Men with G6PD deficiency are, on average, diagnosed with type 2 diabetes four years later than those without the gene variant. But despite this, fewer than one in 50 have been diagnosed with the condition

G6PD deficiency does not cause diabetes, but it makes the widely used HbA1c blood test – which diagnoses and monitors diabetes – appear artificially low. This can mislead doctors and patients, resulting in delayed diabetes diagnosis and treatment.

Early changes during brain development may hold the key to autism and schizophrenia

Photo Credit: Michal Jarmoluk

Researchers at the University of Exeter have created a detailed temporal map of chemical changes to DNA through development and aging of the human brain, offering new insights into how conditions such as autism and schizophrenia may arise.

The team studied epigenetic changes – chemical tags on our DNA that control how genes are switched on or off. These changes are crucial in regulating the expression of genes, guiding brain cells to develop and specialize correctly.

One important mechanism, called DNA methylation, was examined in nearly 1,000 donated human brains, spanning life from just six weeks after conception through to 108 years of age. The researchers focused on the cortex, a region of the brain involved in high-level functions such as thought, memory, perception, and behavior. Correct development of the cortex during early life is important to support healthy brain function after birth.

Decoding the selfish gene, from evolutionary cheaters to disease control

Malaysian stalk-eyed fly (Teleopsis dalmanni).
Photo Credit: Paul Richards

New research is shining a light on one of genetics’ enduring puzzles - how the workings of the so-called “selfish gene” could be harnessed to control harmful insect populations.

Scientists from the University of Sheffield have uncovered how to potentially control harmful insect populations by studying a "selfish gene" that manipulates inheritance

The new research focuses on meiotic drive, a process where a selfish gene gives itself a better chance of being passed on to the next generation, disrupting the normal 50/50 inheritance pattern

By studying the Malaysian stalk-eyed fly, researchers discovered that a selfish gene can damage rival sperm carrying a Y chromosome, leading to a population with far more females than males

Understanding this genetic mechanism could provide a new way to control insects that spread disease and cause food shortages by causing their populations to become unsustainably female-biased

Women of Science: A Legacy of Achievement

Future generations to pursue their passions and break down barriers in the pursuit of knowledge.
Image Credit: Scientific Frontline stock image

Throughout history, women have made groundbreaking contributions to science, despite facing significant societal barriers and a lack of recognition. Their relentless pursuit of knowledge and innovation has shaped our understanding of the world and paved the way for future generations of scientists. This article celebrates the achievements of some of these remarkable women, highlighting their struggles and the impact of their work.

The women featured in this article, along with countless others throughout history, have made invaluable contributions to the advancement of science. Their achievements, often accomplished in the face of adversity and societal barriers, have shaped our understanding of the world and paved the way for future generations of scientists. These women demonstrate the power of perseverance, the importance of challenging established norms, and the profound impact that individual dedication can have on scientific progress. By recognizing and celebrating their legacies, we not only honor their contributions but also inspire future generations to pursue their passions and break down barriers in the pursuit of knowledge.

Genetic research unlocks new ways to prevent and treat multiple long-term conditions

Image Credit: Scientific Frontline stock image

The largest study to date to analyze millions of both genetic and patient records on the long-term health conditions of later life has identified opportunities for new ways to prevent and treat multiple overlapping conditions.  

Currently, nine million people in the UK live with two or more long-term conditions at the same time – known as multimorbidity. Their treatment accounts for half of the NHS budget. 

Led by the University of Exeter Medical School and funded by the Medical Research Council and the National Institute for Health and Care Research, the GEMINI study looked at both genetics and clinical information from more than three million people in the UK and Spain.  

Published in eBioMedicine  research has identified genetic overlaps in 72 long-term health conditions associated with ageing, to identify where specific genes are linked to two or more conditions. With more than 2,500 combinations of conditions analyzed, the program aims to unlock cases where a drug or prevention strategies can prevent or delay the onset of multimorbidity. It also revealed genetic connections that explain why certain conditions may be more likely to co-occur in the same patient. 

Mutations in two gene pairs point to a promising drug target in 5 percent of adult cancers

Illustration Credit: Natalie Velez, Broad Communications

Scientists from the Cancer Dependency Map (DepMap) at the Broad Institute of MIT and Harvard and Columbia University have discovered that about 5 percent of adult cancers rely heavily on a gene called PELO to survive and that disabling the gene kills those cancer cells. These cancers have mutations in one of two genes, FOCAD or TCC37.

The finding, described in Nature, is a new synthetic lethality — a pair of genetic changes that together kill cancer cells. The researchers say that PELO is a promising target, and that genetic testing could identify cancer patients with FOCAD or TCC37 mutations who would benefit from new PELO-targeting drugs.

“These cancers are a huge unmet medical need, because we don’t have effective drugs for them,” said Francisca Vazquez, co-senior author on the study along with postdoctoral researcher Edmond Chan, now an assistant professor at Columbia University. Vazquez is also director of DepMap, which systematically probes cancer cell lines for genetic vulnerabilities. 

“Targeting synthetic lethalities is a good way to expand the repertoire of tumors we’re able to treat,” Vazquez said. “This new synthetic lethality we found shows how powerful the DepMap datasets can be.”

Patricia Borck, a DepMap research scientist in Broad’s Cancer Program, is first author on the study.

Cutting edge technology shows promise in tackling deadly brain tumors

Delivering advanced gene-editing tools directly to the tumor site can improve the body’s defense against glioblastoma
Image Credit: Gemini

A new study led by Khuloud Al Jamal, Professor of Drug Delivery & Nanomedicine, has found an innovative strategy to combat glioblastoma (GB), a fast-growing and aggressive type of brain tumor.

GB is a brain tumor originating in the brain or spinal cord. Despite advances in cancer treatment, it can remain resistant to therapies, including immune checkpoint (ICP) blockade therapies. ICP blockade works by targeting specific proteins on immune or tumor cells to prevent tumors from evading the immune system. While effective in other cancers, this approach has shown limited success in treating GB. The is due to complex interactions between immune cells and glioblastoma stem cells (GSCs), which suppress the immune response and reduce the effectiveness of these therapies.

In the study, published in Advanced Science, Professor Al Jamal and her team revealed how they have taken a novel approach to overcome this challenge by focusing on the mesenchymal subtype of GSCs, which is particularly aggressive and therapy resistant. The study employed lipid nanoparticles (LNPs) — tiny, fat-based carriers — to transport CRISPR RNAs, an advanced gene-editing tool, to GSC and immune cells in therapeutically relevant tumor models. 

WSU researcher pioneers new study model with clues to anti-aging

Jiyue Zhu and a student work in the laboratory.
Photo Credit: Courtesy of Washington State University

Washington State University scientists have created genetically-engineered mice that could help accelerate anti-aging research.

Globally, scientists are working to unlock the secrets of extending human lifespan at the cellular level, where aging occurs gradually due to the shortening of telomeres–the protective caps at the ends of chromosomes that function like shoelace tips to prevent unraveling. As telomeres shorten over time, cells lose their ability to divide for healthy growth, and some eventually begin to die.

But research studying these telomeres at the cellular level has been challenging in humans.

Now, a discovery by a WSU research team published today in the journal Nature Communications has opened the door to using genetically engineered mice.

Led by WSU College of Pharmacy and Pharmaceutical Sciences Professor Jiyue Zhu, the research team has developed mice that have human-like short telomeres, enabling the study of cellular aging as it occurs in the human body and within organs. Normally mice have telomeres that are up to 10 times longer than humans.

A genome-wide atlas of cell morphology reveals gene functions

Human cells imaged using Cell Painting. Cell nuclei are shown in blue, actin filaments in yellow, the endoplasmic reticulum in magenta, golgi bodies in cyan, and mitochondria in green.
Image Credit: Maria Lozada, Neal Lab

Visualizing cells after editing specific genes can help scientists learn new details about the function of those genes. But using microscopy to do this at scale can be challenging, particularly when studying thousands of genes at a time.

Now, researchers at the Broad Institute of MIT and Harvard, along with collaborators at Calico Life Sciences, have developed an approach that brings the power of microscopy imaging to genome-scale CRISPR screens in a scalable way. 

PERISCOPE — which stands for perturbation effect readout in situ via single-cell optical phenotyping — combines two technologies developed by Broad scientists: Cell Painting, which can capture images and key measures of subcellular compartments at scale, and Optical Pooled Screening, which “barcodes” cells and uses CRISPR to systematically turn off individual genes to study their function in those cells. 

The new technique lets scientists study the effects of perturbing over 20,000 genes on hundreds of image-based cellular features. Generating data with this method is more than 10 times less expensive than comparable high-dimensional approaches such as high-throughput single-cell RNA sequencing and can be adapted to study a wide variety of cell types. In Nature Methods, the researchers applied PERISCOPE to execute three whole-genome CRISPR screens to create an open-source atlas of cell morphology.