(Press-News.org) Unlocking the power of nanopores
Poking holes through membranes with atomic accuracy to build pocket-sized ‘molecule detectives’
Brussels/Washington 19/07/2024 - Transmembrane β-barrel pores (TMBs) are extensively used for single-molecule DNA and RNA sequencing. They enable the miniaturization of a wide array of sensing and sequencing applications into portable USB-size devices and point-of-care technologies. A team of Belgian and American researchers has now described a general approach to design TMB pores from scratch with custom shapes and properties, opening up new opportunities for single-molecule analytics. Their results were published in Science.
Rolling out new barrels …
Protein nanopores are the holy grail in the field of analytical biology. These nanometer-sized proteins form regular pores in lipid membranes and are widely used for single-molecule DNA and RNA sequencing. They hold a considerable potential to advance a broad range of sensing and sequencing applications by taking them out of specialized labs and into portable devices. However, current approaches to engineering nanopore sensors are limited to naturally occurring proteins, which have evolved for very different functions and are less than ideal starting points for sensor development.
Research led by the VIB-VUB Center for Structural Biology (Belgium) and the University of Washington School of Medicine (USA) has taken on the challenge of designing these protein ‘barrels’ from scratch, with the ultimate goal of controlling the shape and chemistry on a molecular level. With the help of computational design, the researchers developed methods to design stable nanopore channels with tunable pore shapes, sizes, and conductance. Compared to natural pores, the signal generated by the designed TMBs was remarkably stable and quiet. Collaborators in the laboratory of Sheena Radford (University of Leeds) and Sebastian Hiller (Biozentrum, University of Basel) found that the designs folded into stable 3D structures. This opens the door to designing nanopore channels de novo that are suitable for many applications of interest in research and industry.
“These developments are very exciting. When we started with this idea a few years ago, many people thought it was impossible, because the design and folding of β-sheets is incredibly complex, let alone in lipid membranes. Now we have shown that we can successfully design nanopores with a high success rate, which have stable and reproducible conductance.” - Dr. Anastassia Vorobieva, group leader at the VIB-VUB Center for Structural Biology.
… and putting them to good use
As the next step, the researchers put their design method to the test. Nanopores that can detect very small molecules such as metabolites would be extremely useful tools for metabolomic and diagnostic analysis, which currently require large, specialized lab equipment. The design of functional small-molecule sensors remains challenging because of the complexity of protein-ligand interactions. Hence, the pores need to have a highly complementary shape to the small molecule of interest. A team from the laboratory of UW Medicine biochemistry professor and HHMI Investigator David Baker successfully designed new proteins that can specifically bind small-molecule metabolites. They split the proteins into three parts and fused the parts into the loops of a TMB pore. They found that they could directly detect single-molecule binding events using such constructs.
“This collaboration is a great example of what's possible with protein design. Rather than repurposing biomolecules from nature, we can now create the functions we want from first principles." – Prof. Dr. David Baker, professor at the University of Washington School of Medicine and HHMI investigator.
The positive results prove that nanopore design can complement mass spectrometry and other analytical methods that require big labs and big setups because the technology is smaller and more accessible. Although we are still quite a bit removed from this point, the researchers envision a future in which portable devices with different nanopores can sense a range of metabolites, proteins, and small molecules, or even do biomolecular sequencing.
Funding and Collaborations
The paper, “Sculpting conducting nanopore size and shape through de novo protein design,” appears in the July 19 edition of Science. The research team included scientists from the VUB-VIB Center for Structural Biology, UW Medicine, University of Virginia School of Medicine, University of Leeds, and University of Basel. Computational resources and services used in this work were provided by the VSC (Flemish Supercomputer Center), funded by the Research Foundation - Flanders (FWO) and the Flemish Government. The research team was funded by an FWO-EOS grant.
END
Unlocking the power of nanopores
Poking holes through membranes with atomic accuracy to build pocket-sized ‘molecule detectives’
2024-07-18
ELSE PRESS RELEASES FROM THIS DATE:
Genetic study highlights importance of diversity in understanding health disparities
2024-07-18
PHILADELPHIA— The majority of genetic studies focus on people of European descent, which limits the understanding of how genes influence health in other populations. Researchers at the Perelman School of Medicine at the University of Pennsylvania and the Corporal Michael J. Crescenz VA Medical Center, have partnered with a team of researchers at the Department of Veterans Affairs and the Department of Energy Oak Ridge and Argonne National Laboratories to conduct large-scale studies with diverse groups to better ...
Unhealthy sleep linked to diabetes in a diverse population
2024-07-18
Persistently unhealthy sleep, either not enough or too much, is associated with a significantly increased risk of Type 2 diabetes in a racially and economically diverse adult population, an international team of researchers has reported.
While previous research has linked suboptimal sleep durations to increased diabetes risk, the current report, published in the journal Diabetologia, extended these findings to a large cohort of primarily low-income, middle- to older-age Black and white adults in the southeastern United States.
“Our study contributes new information to support the importance of sleep health in midlife, particularly maintaining ...
Ochsner Health named among America’s Greatest Workplaces by Newsweek
2024-07-18
NEW ORLEANS, La. – For the second consecutive year, Ochsner Health, the leading nonprofit healthcare provider in the Gulf South, has been named one of America’s Greatest Workplaces for 2024 by Newsweek and Plant-A Insights Group. Ochsner’s inclusion on this year’s list highlights the health system’s dedication to delivering excellence in inclusivity, employee empowerment and innovative culture.
Newsweek and Plant-A Insights Group recognize the America’s Greatest Workplaces in the United States by conducting a large-scale employer ...
Is climate change keeping patients from vital doctor appointments?
2024-07-18
Temperature extremes, becoming increasingly frequent due to growing global climate change, are associated with higher rates of missed primary care appointments, according to a recently published study from Drexel University researchers in the American Journal of Preventive Medicine.
The researchers found that rates of missed appointments increased by 0.72% for every 1°F decrease in daily maximum temperatures below 39°F and increased by 0.64% for every 1°F increase above 89°F. Patients 65 and older and those with ...
How pollution may remain in water after oil spill cleanups
2024-07-18
Oil drops from underwater oil spills can break into tinier droplets at the surface that remain suspended in the water, according to research from the University of Illinois Chicago. That means cleanups after disasters like the Deepwater Horizon spill may be removing less oil from the environment than was thought.
Because oil is lighter than water, it rises through the ocean after spills, which are usually caused by leaking underwater pipelines or sometimes by natural processes. It was believed that when these ...
World’s first method: Successful surgery for a rare congenital heart disease “scimitar syndrome”
2024-07-18
Scimitar syndrome, a rare congenital heart disease, involves an anomalous pulmonary venous return where the right pulmonary veins return to the inferior vena cava instead of the left atrium. It is mainly diagnosed in infants, with an estimated prevalence of 1–3 per 100,000 births. Delayed treatment can lead to pulmonary hypertension, right heart failure, respiratory failure, heart arrhythmia, and growth disorders.
This syndrome is characterized by anomalous pulmonary venous drainage to the inferior vena cava, and the usual surgical repair involves re-implanting the right pulmonary veins (scimitar vein) to the left atrium or creating an intra-atrial tunnel to ...
Major computing society endorses efforts to make digital accessibility part of the Americans with Disabilities Act
2024-07-18
The Association for Computing Machinery’s US Technology Policy Committee (USTPC) has released a Statement in Support of Mandatory Comprehensive Digital Accessibility Regulations. The US Department of Justice recently updated the Americans with Disabilities Act (ADA), a civil rights law that prohibits discrimination based on disability, with requirements for the accessibility of web content and mobile applications. The aim of the revision to the ADA is to ensure that services, programs and activities provided by state and local governments online ...
When you eat may impact your overall health, nutrition experts say
2024-07-18
Philadelphia, July 18, 2024 – Accumulating evidence on the effect of the time of eating in relation to our circadian rhythm and metabolism shows that when we eat may influence our overall health and well-being. A special issue of the Journal of the Academy of Nutrition and Dietetics (JAND) on chrononutrition, published by Elsevier, examines the effects of various fasting regimens and covers safety considerations and practical guidance.
The field of chrononutrition is gaining traction as it explores the relationship between temporal eating patterns, circadian rhythms, and metabolism for optimal health.
Guest Editor Krista Varady, PhD, Department of Kinesiology and Nutrition, ...
Researcher receives NASA funding to study ozone pollution
2024-07-18
NORMAN, OKLA. – University of Oklahoma professor Chenghao Wang has received three years of funding through the National Aeronautics and Space Administration Early Career Investigator Program in Earth Science. Wang, an assistant professor in both the OU School of Meteorology and the Department of Geography and Environmental Sustainability, will study compound heat and ozone pollution episodes in urban environments.
Heat waves and air pollution are two increasingly occurring challenges that disproportionately impact urban areas. When multiple stressor events happen simultaneously, these compound events can have more significant impacts than isolated events. ...
New ECDC Director Pamela Rendi-Wagner emphasises importance of restoring and reinforcing public trust in science after pandemic, in editorial for Eurosurveillance
2024-07-18
In an editorial for the scientific journal Eurosurveillance, the incoming ECDC Director Dr Pamela Rendi Wagner outlined her vision for the European Union’s public health agency, highlighting the mounting challenges to public health after the COVID-19 pandemic, including war in Europe, climate change, and increasing social inequalities. She also emphasised the importance of reinforcing and restoring public trust in science.
Current challenges in public health
“War, flooding and the effects of ...
LAST 30 PRESS RELEASES:
Insulin resistance is linked to over 30 diseases – and to early death in women, study of people in the UK finds
Innovative semaglutide hydrogel could reduce diabetes shots to once a month
Weight loss could reduce the risk of severe infections in people with diabetes, UK research suggests
Long-term exposure to air pollution and a lack of green space increases the risk of hospitalization for respiratory conditions
Better cardiovascular health in early pregnancy may offset high genetic risk
Artificial intelligence method transforms gene mutation prediction in lung cancer: DeepGEM data releases at IASLC 2024 World Conference on Lung Cancer
Antibody–drug conjugate I-DXd shows clinically meaningful response in patients with extensive-stage small cell lung cancer
IASLC Global Survey on biomarker testing reveals progress and persistent barriers in lung cancer biomarker testing
Research shows pathway to developing predictive biomarkers for immune checkpoint inhibitors
Just how dangerous is Great Salt Lake dust? New research looks for clues
Maroulas appointed Associate Vice Chancellor, Director of AI Tennessee
New chickadee research finds cognitive skills impact lifespan
Cognitive behavioral therapy enhances brain circuits to relieve depression
Terasaki Institute awarded $2.3 Million grant from NIH for organ transplantation research using organs-on-a-chip technology
Atoms on the edge
Postdoc takes multipronged approach to muon detection
Mathematical proof: Five satellites needed for precise navigation
Scalable, multi-functional device lays groundwork for advanced quantum applications
Falling for financial scams? It may signal early Alzheimer’s disease
Integrating MRI and OCT for new insights into brain microstructure
Designing a normative neuroimaging library to support diagnosis of traumatic brain injury
Department of Energy announces $68 million in funding for artificial intelligence for scientific research
DOE, ORNL announce opportunity to define future of high-performance computing
Molecular simulations, supercomputing lead to energy-saving biomaterials breakthrough
Low-impact yoga and exercise found to help older women manage urinary incontinence
Genetic studies reveal new insights into cognitive impairment in schizophrenia
Researcher develops technology to provide cleaner energy and cleaner water
Expect the unexpected: nanoscale silver unveils intrinsic self-healing abilities
nTIDE September 2024 Jobs Report: Gains in employment for people with disabilities appear to level off after reducing gaps with non-disabled workers
Wiley enhances NMR Spectral Library Collection with extensive new databases
[Press-News.org] Unlocking the power of nanoporesPoking holes through membranes with atomic accuracy to build pocket-sized ‘molecule detectives’