Women of Science: A Legacy of Achievement

Future generations to pursue their passions and break down barriers in the pursuit of knowledge.
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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

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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.

Eight Psychiatric Disorders Share the Same Genetic Causes

Image Credit: Won Lab

Building off previous groundbreaking research, a new study identifies specific genetic variants that have significant impacts on brain development and are shared across eight different psychiatric disorders. Targeting these variants could pave the way for treatments that address multiple conditions at once.

Psychiatric disorders often overlap and can make diagnosis difficult. Depression and anxiety, for example, can coexist and share symptoms. Schizophrenia and anorexia nervosa. Autism and attention deficit/hyperactivity disorder, too. But, why?

Life experiences, environment, and genetics can all influence psychiatric disorders, but much of it comes down to variations in our genetics. Over the past few years, scientists in the field of psychiatric genetics have found that there are common genetic threads that may be linking and causing coexisting psychiatric disorders.

In 2019, researchers at the Psychiatric Genomics Consortium, Harvard University, and the UNC School of Medicine identified 136 “hot spots” within the genome that are associated with eight psychiatric disorders. Among them, 109 hot spots were shared among multiple disorders, or “pleiotropic”. However, it was not clear at the time how genetic variations within these hot spots differed from those that only have roles in only one disorder.

Gene editing extends lifespan in mouse model of prion disease

Broad Communications Eric Minikel and Sonia Vallabh run a lab with a singular focus: preventing and treating prion disease within their lifetime.
Photo Credit: Maria Nemchuk

Researchers at the Broad Institute of MIT and Harvard have developed a gene-editing treatment for prion disease that extends lifespan by about 50 percent in a mouse model of the fatal neurodegenerative condition. The treatment, which uses base editing to make a single-letter change in DNA, reduced levels of the disease-causing prion protein in the brain by as much as 60 percent. 

There is currently no cure for prion disease, and the new approach could be an important step towards treatments that prevent the disease or slow its progression in patients who have already developed symptoms. A base-editing approach could also likely be a one-time treatment for all prion disease patients regardless of the genetic mutation causing their disease. 

The work, led by Broad senior group leaders Sonia Vallabh and Eric Minikel, as well as Broad core institute member David Liu, is the first demonstration that lowering levels of the prion protein improves lifespan in animals that have been infected with a human version of the protein. The findings appear in Nature Medicine.

Chornobyl Dogs’ Genetic Differences Not Due to Mutation

Photo Credit: Norman Kleiman

Radiation-induced mutation is unlikely to have induced genetic differences between dog populations in Chornobyl City and the nearby Chornobyl Nuclear Power Plant (NPP), according to a new study in PLOS ONE from North Carolina State University and Columbia University Mailman School of Public Health. The study has implications for understanding the effects of environmental contamination on populations over time.

“We have been working with two dog populations that, while separated by just 16 kilometers, or about 10 miles, are genetically distinct,” says Matthew Breen, Oscar J. Fletcher Distinguished Professor of Comparative Oncology Genetics at NC State. “We are trying to determine if low-level exposure over many years to environmental toxins such as radiation, lead, etcetera, could explain some of those differences.” Breen is the corresponding author of the study.

Previously, the team had analyzed genetic variants distributed across the genome and identified 391 outlier regions in the dogs that differed between the two populations. Some of these regions contained genes associated specifically with repair of DNA damage. In this new study, the researchers conducted a deeper dive into the genomes of the dogs to detect evidence of mutations that may have accumulated over time.

First-of-its-kind integrated dataset enables genes-to-ecosystems research

DOE national laboratory scientists led by Oak Ridge National Laboratory have developed the first tree dataset of its kind, bridging molecular information about the poplar tree microbiome to ecosystem-level processes.
Illustration Credit: Andy Sproles/ORNL, U.S. Dept. of Energy

The first-ever dataset bridging molecular information about the poplar tree microbiome to ecosystem-level processes has been released by a team of Department of Energy scientists led by Oak Ridge National Laboratory. The project aims to inform research regarding how natural systems function, their vulnerability to a changing climate, and ultimately how plants might be engineered for better performance as sources of bioenergy and natural carbon storage.

The data, described in Nature Publishing Group’s Scientific Data, provides in-depth information on 27 genetically distinct variants, or genotypes, of Populus trichocarpa, a poplar tree of interest as a bioenergy crop. The genotypes are among those that the ORNL-led Center for Bioenergy Innovation previously included in a genome-wide association study linking genetic variations to the trees’ physical traits. ORNL researchers collected leaf, soil and root samples from poplar fields in two regions of Oregon — one in a wetter area subject to flooding and the other drier and susceptible to drought. 

Details in the newly integrated dataset range from the trees’ genetic makeup and gene expression to the chemistry of the soil environment, analysis of the microbes that live on and around the trees and compounds the plants and microbes produce.

The dataset “is unprecedented in its size and scope,” said ORNL Corporate Fellow Mitchel Doktycz, section head for Bioimaging and Analytics and project co-lead. “It is of value in answering many different scientific questions.” By mining the data with machine learning and statistical approaches, scientists can better understand how the genetic makeup, physical traits and chemical diversity of Populus relate to processes such as cycling of soil nitrogen and carbon, he said. 

Single genomic test could speed up diagnoses for rare genetic diseases

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A new approach to analyzing exome sequencing data reliably detects large-scale genetic changes and could reduce the number of genetic tests a child might need.

A single genetic test could potentially replace the current two-step approach to diagnosing rare developmental disorders in children, enabling earlier diagnoses for families and saving the NHS vital resources.

Researchers from the University of Exeter, along with collaborators at the Wellcome Sanger Institute, and the University of Cambridge, reassessed genetic data from nearly 10,000 families from the Deciphering Developmental Disorders study.

In a new study, recently published in Genetics in Medicine, they show for the first time that using exome sequencing – which reads only protein-coding DNA – is as accurate, if not better, than standard microarrays at identifying disease-causing structural genetic variations.

Its adoption offers hope for faster and more accurate diagnoses of rare genetic diseases. It could also deliver substantial cost savings for the NHS, though more training is needed for specialists to generate and analyze the data, say researchers.

Cystic fibrosis: why infections persist despite therapy

The anchor points present on the surface of the airways in cystic fibrosis (left image, in red) decrease when the balance between the two cell signaling pathways is restored (right image).
Image Credit: Marc Chanson et al, 2024

Cystic fibrosis is a genetic disease that causes serious and sometimes fatal respiratory and digestive disorders. A new treatment, available since 2020, improves lung function and quality of life. However, it does not always eradicate the bacteria responsible for respiratory infections. By studying 3D models of human lung cells, scientists at the University of Geneva (UNIGE) discovered that this drug does not prevent the development on the surface of the respiratory tract of ''docking stations'' to which bacteria attach themselves to infect the body. These docking stations result from a disruption in the signals involved in cell development in the respiratory system. By combining the current treatment with other molecules, it may be possible to restore cell balance and thus better prevent bacterial infections. These results are published in the American Journal of Respiratory Cell and Molecular Biology.

Cystic fibrosis is the most common genetic disease. Each year, it affects one in every 3,300 newborns in Switzerland. Mutations in the gene responsible for the CFTR protein cause the secretion of excessively thick mucus, which obstructs the airways. Although a triple therapy, available in Switzerland since 2020, has improved the quality of life of people with cystic fibrosis, it is not suitable for all those affected and does not always prove effective.

New sunflower family tree reveals multiple origins of flower symmetry

A new sunflower family tree reveals that flower symmetry evolved multiple times independently. Chrysanthemum lavandulifolium, on the upper left, and Artemisia annua, upper right, are closely related species from the same tribe; the former has bilaterally symmetric flowers — the rays — and the latter does not. Rudbeckia hirta, lower left, from the sunflower tribe has bilaterally symmetric flowers, and Eupatorium chinense, lower right, from the Eupatorieae tribe does not; these two tribes are closely related groups. A sunflower, center, shows flowers with bilateral symmetry — the large petal-like flowers in the outer row — and without bilateral symmetry — the small flowers in the inner rows.
Photo Credits: Guojin Zhang, Ma laboratory / Pennsylvania State University
(CC BY-NC-ND 4.0 DEED)

The sunflower family tree revealed that flower symmetry evolved multiple times independently, a process called convergent evolution, among the members of this large plant family, according to a new analysis. The research team, led by a Penn State biologist, resolved more of the finer branches of the family tree, providing insight into how the sunflower family — which includes asters, daisies and food crops like lettuce and artichoke — evolved.

A paper describing the analysis and findings, which researchers said may help identify useful traits to selectively breed plants with more desirable characteristics is available online and will be published in an upcoming print edition of the journal Plant Communications.

“Convergent evolution describes the independent evolution of what appears to be the same trait in different species, like wings in birds and bats,” said Hong Ma, Huck Chair in Plant Reproductive Development and Evolution, professor of biology in the Eberly College of Science at Penn State and the leader of the research team. “This can make it difficult to determine how closely related two species are by comparing their traits, so having a detailed family tree based on DNA sequence is crucial to understanding how and when these traits evolved.”

Scientists discover potential treatment approaches for polycystic kidney disease

cientists would like to know how cysts form in polycystic kidney disease (PKD). Here, they compared two 3-D mini-kidney models. On the left, a model shows a mini kidney with a gene mutation that causes cysts to form. On the right, researchers used gene editing to correct a gene mutation, preventing the development of cysts.
Image Credit: Vishy, et al., Cell Stem Cell 2024

Researchers have shown that dangerous cysts, which form over time in polycystic kidney disease (PKD), can be prevented by a single normal copy of a defective gene. This means the potential exists that scientists could one day tailor a gene therapy to treat the disease. They also discovered that a type of drug, known as a glycoside, can sidestep the effects of the defective gene in PKD. The discoveries could set the stage for new therapeutic approaches to treating PKD, which affects millions worldwide. The study, partially funded by the National Institutes of Health (NIH), is published in Cell Stem Cell.

Scientists used gene editing and 3-D human cell models known as organoids to study the genetics of PKD, which is a life-threatening, inherited kidney disorder in which a gene defect causes microscopic tubes in the kidneys to expand like water balloons, forming cysts over decades. The cysts can crowd out healthy tissue, leading to kidney function problems and kidney failure. Most people with PKD are born with one healthy gene copy and one defective gene copy in their cells.

“Human PKD has been so difficult to study because cysts take years and decades to form,” said senior study author Benjamin Freedman, Ph.D., at the University of Washington, Seattle. “This new platform finally gives us a model to study the genetics of the disease and hopefully start to provide answers to the millions affected by this disease.”

Scientists identify rare gene variants which confer up to 6-fold increase in risk of obesity

Photo Credit: Mart Production

The discovery of rare variants in the genes BSN and APBA1 are some of the first obesity-related genes identified for which the increased risk of obesity is not observed until adulthood.

The study, published in Nature Genetics, was led by researchers at the Medical Research Council (MRC) Epidemiology Unit and the MRC Metabolic Diseases Unit at the Institute of Metabolic Science, both based at the University of Cambridge.

The researchers used UK Biobank and other data to perform whole exome sequencing of body mass index (BMI) in over 500,000 individuals.

They found that genetic variants in the gene BSN, also known as Bassoon, can raise the risk of obesity as much as six times and was also associated with an increased risk of non-alcoholic fatty liver disease and of type 2 diabetes.

The Bassoon gene variants were found to affect 1 in 6,500 adults, so could affect about 10,000 people in the UK.

‘Exhausted’ immune cells in healthy women could be target for breast cancer prevention

Photo Credit: Angiola Harry

Everyone has BRCA1 and BRCA2 genes, but mutations in these genes - which can be inherited - increase the risk of breast and ovarian cancer.

The study found that the immune cells in breast tissue of healthy women carrying BRCA1 or BRCA2 gene mutations show signs of malfunction known as ‘exhaustion’. This suggests that the immune cells can’t clear out damaged breast cells, which can eventually develop into breast cancer.

This is the first time that ‘exhausted’ immune cells have been reported in non-cancerous breast tissues at such scale - normally these cells are only found in late-stage tumors.

The results raise the possibility of using existing immunotherapy drugs as early intervention to prevent breast cancer developing, in carriers of BRCA1 and BRCA2 gene mutations.

The researchers have received a ‘Biology to Prevention Award’ from Cancer Research UK to trial this preventative approach in mice. If effective, this will pave the way to a pilot clinical trial in women carrying BRCA gene mutations.

“Our results suggest that in carriers of BRCA mutations, the immune system is failing to kill off damaged breast cells - which in turn seem to be working to keep these immune cells at bay,” said Professor Walid Khaled in the University of Cambridge’s Department of Pharmacology and Wellcome-MRC Cambridge Stem Cell Institute, senior author of the report.

New Genetic Analysis Tool Tracks Risks Tied to CRISPR Edits

UC San Diego researchers have created a new system that reveals specific categories of potentially risky mutations resulting from CRISPR edits. This high magnification image reveals CRISPR-based DNA transcription of the homothorax gene in fruit fly embryos.
Image Credit: Bier Lab, UC San Diego

Since its breakthrough development more than a decade ago, CRISPR has revolutionized DNA editing across a broad range of fields. Now scientists are applying the technology’s immense potential to human health and disease, targeting new therapies for an array of disorders spanning cancers, blood conditions and diabetes.

In some designed treatments, patients are injected with CRISPR-treated cells or with packaged CRISPR components with a goal of repairing diseased cells with precision gene edits. Yet, while CRISPR has shown immense promise as a next-generation therapeutic tool, the technology’s edits are still imperfect. CRISPR-based gene therapies can cause unintended but harmful “bystander” edits to parts of the genome, at times leading to new cancers or other diseases.

Next-generation solutions are needed to help scientists unravel the complex biological dynamics behind both on- and off-target CRISPR edits. But the landscape for such novel tools is daunting, since intricate bodily tissues feature thousands of different cell types and CRISPR edits can depend on many different biological pathways.

Blood analysis predicts sepsis and organ failure in children

Photo Credit: Edward Jenner

University of Queensland researchers have developed a method to predict if a child is likely to develop sepsis and go into organ failure.

Associate Professor Lachlan Coin from UQ’s Institute for Molecular Bioscience said sepsis was a life-threatening condition where a severe immune response to infection causes organ damage.

“Our research involved more than 900 critically ill children in the emergency departments and intensive care units of four Queensland hospitals,” Dr Coin said.

“Blood samples were taken from these patients at the acute stage of their infection, and we analyzed which genes were activated or deactivated.

“We were able to identify patterns of gene expression which could predict whether the child would develop organ failure within the next 24 hours, as well as whether the child had a bacterial or viral infection or a non-infectious inflammatory syndrome.”

Professor Luregn Schlapbach from UQ’s Child Health Research Centre said sepsis is best treated when recognized early, so the finding could help clinicians in the future.

Mystery of unexplained kidney disease revealed to patients

Professor John Sayer
“What we are now able to do is give some patients a precise diagnosis, which allows their investigations, treatment and management to be tailored to their needs for the best possible outcomes.”
Photo Credit: Courtesy of Newcastle University

Scientists have identified a new method of analyzing genomic data in a major discovery that means patients with unexplained kidney failure are finally getting a diagnosis.

Experts at Newcastle University have worked with data from Genomics England 100,000 Genomes Project to establish a diagnosis in patients with unexplained kidney failure.

There are numerous reasons for kidney failure, which if left untreated is life-threatening, but often patients do not get a precise diagnosis which can make their best course of treatment unclear.

Missing genetic data

Research, published in the Genetics in Medicine Open, has now revealed that for these patients areas in their genome are missing so are not detected as faulty when using the routine genetic pipelines to analyze data. 

Scientists say that as this missing gene has now been identified, and mutations within it found, they have been able to classify this as NPHP1-related kidney failure.

Researchers roll out a more accurate way to estimate genetic risks of disease

Illustration Credit: Ricardo Job-Reese, Broad Communications.

Researchers have developed statistical tools called polygenic risk scores (PRSs) that can estimate individuals’ risk for certain diseases with strong genetic components, such as heart disease or diabetes. However, the data on which PRSs are built is often limited in diversity and scope. As a result, PRSs are less accurate when applied to populations that differ demographically from the PRS training data.

A new scoring approach featured in Cell Genomics and developed by researchers at the Broad Institute of MIT and Harvard and Massachusetts General Hospital (MGH) uses a comprehensive approach to generate more accurate and informative PRSs. Aptly named PRSmix due to its ability to “mix” all previously developed PRSs for a given trait, the approach generates scores that estimate a patient’s genetic disease risk more accurately than PRSs generated from individual studies.

“A major challenge with PRSs is that they’re derived in one population and then unleashed broadly with the assumption that the scores can be generalized,” explained Pradeep Natarajan, the study’s corresponding author. Natarajan is an associate member in Broad's Cardiovascular Disease Initiative and director of preventive cardiology at MGH. “The overall motivation for this work is to better identify individuals who are prematurely at high risk for heritable conditions.”