Air pollution increases in South East Asia, combined with pollution cuts in Europe, may have had an important influence on European and Asian weather patterns in recent decades, new research has found.

Analysis of weather records and climate models by scientists at the University of Reading revealed that changes in air pollution levels in the two regions were likely the primary driving force behind changing atmospheric conditions that favored prolonged summer extremes in Europe, as well as causing dry spells in Central Asia.

New research shows that the air pollution changes during 1979-2019 reduced the temperature gradient between the two regions, significantly weakening the jet stream over Asia.

These high-altitude winds have a strong influence on atmospheric circulation in the Northern Hemisphere, and shape weather across Europe and other mid-latitude areas.

Dr. Buwen Dong, an NCAS scientist at the University of Reading, said: “Our findings suggest changes to air pollution had a greater influence on Northern Hemisphere summer weather than we thought.

“The research counters previous suggestions that the weakening of the summer jet stream was the result of rapid warming in the Arctic due to greenhouse gas emissions. It highlights another significant role human activity plays in driving extreme weather over vast regions.”

Air pollution is known to have a direct impact on surface temperatures since the pollution particles prevent heat from the sun from penetrating the ground.

Increases in pollution in China and other areas of South and East Asia during the past 40 years, therefore, resulted in lower surface temperatures, while cuts in Europe led to clearer skies and hotter temperatures.

Temperature changes in different latitudes reduced vertical wind shear and therefore weakened the summertime Eurasian subtropical westerly jet - the ribbon of wind which extends east over Central Asia and northern China from the North Atlantic Jet Stream – by 7% over the period.

The researchers looked at the effect of greenhouse gases and pollution particles separately and found that the former causes a strengthening of the jet stream, but was overpowered by the impacts of air pollution.

Dr. Dong said: “As Southeast Asian countries fulfill commitments to cut their air pollution levels over the coming decades, we would expect to see the jet stream strengthen over Eurasia once again, potentially reducing the likelihood of prolonged heatwaves but increasing the likelihood of strong cyclones in mid-latitudes.”

With a $2 million recruitment grant from the Cancer Prevention and Research Institute of Texas (CPRIT), a University of Houston researcher is setting up a lab to develop drugs that will work on traditionally undruggable targets in cancer. Gül Zerze, assistant professor in the William A. Brookshire Department of Chemical and Biomolecular Engineering at the UH Cullen College of Engineering, is one of 12 cancer researchers recruited to Texas by CPRIT last November.  

Zerze’s initial target is breast cancer. 

"One out of nearly six Texas women diagnosed with breast cancer will die of the disease. Importantly, Texan women of color are disproportionately impacted by the high mortality rate compared to white Texan women (41% higher mortality rate reported for Black Texan women in 2016). This high mortality rate, despite the substantial efforts made for early diagnosis, calls for better therapeutics urgently,” said Zerze, whose research will also be expanded more broadly to address other cancers. 

The CPRIT recruitment grants for the latest class, totaling $38 million, are meant to “form a critical ecosystem of distinguished cancer-fighting talent” in Texas. Zerze was persuaded to come to UH from Princeton University where she was a postdoctoral researcher specializing in computational modeling and simulations of a special class of proteins called intrinsically disordered proteins (IDPs).  

The vast majority (approximately 70%) of proteins implicated in human cancers are either IDPs or have large intrinsically disordered regions, and many of these targets are considered ‘undruggable’ due to the scarcity of high-resolution methods that can offer a fundamental understanding of them. 

“Computational and data science methodologies offer a promising avenue to fill in this gap to enable developing drugs against these traditionally undruggable targets,” said Zerze, whose methodology will include rapid screening.  

Despite the significant progress made in cancer treatment options in the last 20 years, many cancer targets have still yet to be drugged. Among those holding promise are transcription factors (TFs), which are proteins involved in converting (or transcribing) DNA into RNA. TFs contain large amounts of disordered proteins which participate in transcriptional condensates that form via liquid-like phase separation (LLPS).  

“Transcriptional condensates are shown to be aberrant in tumor cells, but the progress to develop drugs against TFs that participate in LLPS has been limited by the extremely dynamic nature of activation domains of TFs. We are developing a computational platform that will enable discovering drugs against these aberrant condensates by systematically interrogating the way transcription factors form, through the liquid-like phase separation of intrinsically disordered regions,” said Zerze. 

Through collaborations within the University and the MD Anderson Cancer Center, the drug candidates will be rapidly tested.  

“The ideas proposed here will save lives and the products that will come out of this project have a great potential for commercialization and founding companies to contribute to the Texas economy,” said Zerze. 

The international AEG firm’s sixth Florida office will support the collaborative advancement of research, education, and economic development, and will support Woolpert’s expansion throughout the state. 

Woolpert has opened an office in St. Petersburg, Fla., that will focus on maritime, defense technology, and geospatial intelligence. The office is located in the St. Pete Innovation District (SPID) and is part of its new St. Petersburg Maritime and Defense Technology Hub, which is holding its ribbon-cutting event today. SPID is a public-private partnership that aims to foster job growth, economic development, learning, and inspiration by bringing innovative people and organizations together.

SPID has established the largest collection of marine science, oceanographic and environmental research agencies and institutions in the Southeast. Its Maritime and Defense Technology Hub assembles innovators from industry, government, and academic organizations that can utilize state and federal funding to advance critical marine science and defense technology solutions.

Woolpert is a global leader in the collection and processing of high-resolution topographic and bathymetric lidar and imagery, acoustic hydrographic services, and marine surveys. The international architecture, engineering, and geospatial (AEG) firm specializes in delivering geospatial data and innovative hybrid technologies to defense and federal intelligence communities. In 2021, Woolpert augmented its capabilities by acquiring two geospatial firms, AAM and Optimal GEO, and earning a patent for developing revolutionary new topo-bathy lidar technologies. Last month, the firm acquired eTrac Inc., a vessel-based hydrographic survey and marine technology firm.

In Florida, Woolpert has supported state, local, and federal government projects for decades, helping agencies solve their most important infrastructure, maritime and hydrographic challenges. Woolpert President and CEO Scott Cattran said the Hub, which is Woolpert’s sixth Florida office, will serve as his new office and that of several senior vice presidents to support the firm’s expansion in the region and the state. Woolpert’s work at the Hub also will contribute to SPID’s Grow Smarter strategy to elevate education, equity, and entrepreneurship.

“This kind of diverse collaboration is key to the nation’s short- and long-term advancement of progressive ideas and real-world solutions,” Cattran said. “Woolpert has worked with several SPID partners and has found success within this type of setting, from joint ventures to research and development teams to public-private-academic partnerships, and we are looking forward to what we can all accomplish within this dynamic ecosystem.”

Cambridge Crystallographic Data Centre (CCDC), Exscientia, and Oxford University collaborate on an automated, quantitative method for informing the design of compound selectivity across protein families

The amount of structural data on protein drug targets continues to grow. However, successfully mining this data to form testable hypotheses that drive drug discovery can prove challenging. Selectivity for the target protein is a crucial property in the development of new therapeutics. In a recent paper in the Journal of Chemical Information and Modeling, authors from the CCDC, Exscientia, and Oxford University show how an automated process leveraging “ensemble hotspot maps” can identify key structural differences that contribute to the selectivity of a compound for one protein over another. 

The power of hotspot mapping to advance drug design

Hotspot mapping quantifies the propensity for compounds to exploit interactions in a preferred binding site—providing a 3D grid of data to help score and prioritize compounds. The power of this method lies in how it finds key interactions during early-phase drug discovery and then distills the information into easily interpretable results. Chris Radoux is Head of Structural Bioinformatics at Exscientia and a co-author on the paper.

“Adding hotspot maps early in a drug discovery project can provide a molecular blueprint using the protein structure alone,” says Radoux. “This can be used to help determine how druggable a given pocket of a target protein is and to prioritize fragment starting points for compound design. The highest scoring interactions can then be used to guide computational methods and algorithms.”

Hotspot maps drive cohesive drug design

This approach automates analysis across a protein family, as proteins in the same family often have similar binding sites. According to Mihaela D Smilova, co-author and postgraduate researcher at the Centre for Medicines Discovery at Oxford University, selectivity profiles in both the complete proteome—and within the target protein family—must be understood to develop safe and effective drugs. Interactions with unrelated target proteins can lead to unwanted side effects and toxicity, she says. However, effective drugs often exploit the benefits of “polypharmacology.”

“Introducing polypharmacology, or the ability to modulate multiple targets, may help to prevent the development of resistant disease phenotypes,” says Smilova. “Consequently, a successful drug candidate has a finely tuned selectivity profile within its target family—interacting with targets that positively impact the disease phenotype and avoiding interactions that lead to unwanted side effects.”

Using hotspot maps as inputs for computational workflows means researchers can rapidly explore the chemical space.

“This saves time by summarizing the information and presenting it in a way that is both interpretable by medicinal chemists and can be used in further computational analyses,” says Smilova.

Leveraging real-world, empirical data for reliability

The script used to generate the hotspot maps is a Python package called, “Hotspots API,” which leverages the data in the Cambridge Structural Database (CSD) via CCDC’s IsoStar library of interactions. The CSD is the world’s repository for small-molecule organic and metal-organic crystal structures—containing over 1.1 million structures from x-ray and neutron diffraction analyses. IsoStar is a web application that uses the CSD to generate thousands of interactive 3D scatterplots that show the probability of occurrence and spatial characteristics of interactions between pairs of chemical functional groups. Dr. Jason Cole is a Senior Research Fellow at CCDC.

“Using CSD data for this type of analysis provides different insights from energy-calculation-based methods, as the interactions observed in the CSD are influenced by more than their strength,” says Cole.

Impacts of the study

Exscientia is a global leader in pharma tech, which sits at the interface of advanced AI applications and complex drug discovery. They have implemented the hotspot mapping in-house within multiple drug discovery programs and use it to guide target validation and drug design. In addition, a research team at the University of Cambridge recently published in Nature how they used fragment hotspot mapping to identify structures that may assist in designing DNA-dependent protein kinase catalytic subunit inhibitors, which show potential as cancer therapeutics.