Large-scale brain epigenetics study provides new insights into dementia

June 10, 2021

The largest study of its kind has unveiled new insights into how genes are regulated in dementia, including discovering 84 new genes linked to the disease.

Researchers from the ASU-Banner Neurodegenerative Disease Research Center (NDRC) join international colleagues, led by the University of Exeter, to investigate the molecular underpinnings of Alzheimer’s and other neurodegenerative diseases.   Diego Mastroeni, a contributor to the new study published in Nature Communications, is a researcher in the ASU-Banner Neurodegenerative Disease Research Center. Download Full Image

The collaboration combined and analysed data across six different studies, in a meta-analysis published in Nature Communications. These studies had used brain samples from people who had died with Alzheimer’s disease.

“This manuscript is the first meta-analyses of Alzheimer’s disease pathology, highlighting numerous cortical regions in nearly 1,500 subjects,” said Diego Mastroeni, a researcher at the NDRC and collaborator on the new study. “This is an invaluable resource and will be fundamental in understanding underlying mechanisms that regulate which genes are poised for expression or which genes are not.”

Fellow NDRC researchers Danielle Brokaw and Paul Coleman also contributed to the paper.

The project, funded by the Alzheimer’s Society and the Medical Research Council and supported by the National Institutes for Health, looked at an epigenetic mark called DNA methylation at nearly half a million sites in the genome.

Epigenetic processes control the extent to which genes are switched on and off, allowing for fine-tuned gene expression across the different cell types and tissues that make up the human body. Importantly, unlike the genes themselves, which remain stable throughout life, epigenetic processes that modify the behaviour of genes can be influenced by environmental factors, making them potentially reversible and a possible route to new treatments.

The study looked at epigenetic patterns across the genome, in a number of different regions of the brain. The team then related the amount of DNA methylation to the quantity of neurofibrillary tangles within the brain — an important hallmark of the severity of Alzheimer’s disease.

The team explored various regions of the brain that were selectively affected in Alzheimer’s disease before looking for common changes across these cortical regions. They identified 220 sites in the genome, including 84 new genes, which showed different levels of DNA methylation in the cortex in individuals with more severe Alzheimer’s disease, which weren’t seen in another area of the brain, called the cerebellum.

The research demonstrates that a subset of 110 of these affected sites, found in two independent datasets, could be used to distinguish whether a brain sample had high or low levels of disease, with more than 70% accuracy. This suggests that epigenetic changes in the brain in Alzheimer’s disease are very consistent.

Professor Katie Lunnon, of the University of Exeter, who led the research, said: “Our study is the largest of its kind, giving important insights into genomic areas that could one day provide the key to new treatments. The next step for this work is to explore whether these epigenetic changes lead to measurable changes in the levels of genes and proteins being expressed. This will then allow us to explore whether we could repurpose existing drugs that are known to alter the expression levels of these genes and proteins, to effectively treat dementia.”

The study included a number of international collaborators from the U.S. (Columbia University and Mount Sinai School of Medicine in New York, Rush University Center in Chicago, Arizona State University), and Europe (Maastricht University in Netherlands, University of Saardland, Germany).

“This manuscript is a testament of the kind of collaborative efforts we at ASU and the NDRC are so proud of,” Mastroeni said. “Reaching out across the globe to get involved in fantastic work like this is what we need to do if we are to ever find a cure.”  

Richard Harth

Science writer, Biodesign Institute at ASU


ASU, Siemens amplify curriculum for industry-bound students

June 10, 2021

Global technology leader Siemens is one of the driving forces behind engineering workforce development in the Phoenix area. The company’s support of Arizona State University’s eProjects program is helping to propel engineering student readiness at The Polytechnic School, one of the six Ira A. Fulton Schools of Engineering at ASU.

For nearly 10 years, the eProjects program at The Polytechnic School has facilitated industry and student collaborations, allowing both groups to work together on real-world projects to develop or improve a product or process to broadly advance engineering capabilities. Siemens capstone project Engineering senior Jean-Francois Enriquez is using Siemens hardware to operate a digital twin machine as part of his senior design capstone project. Photo by Sona Srinarayana/ASU Download Full Image

Through this mutually beneficial partnership, industry-bound students gain applicable workforce skills and technical knowledge while industry partners gain innovative engineering solutions, intellectual property for operational implementation and opportunities for recruitment.

“This program is successful because industry partners challenge and guide our seniors through tangible engineering demands and share their experience and wisdom along the way,” said Tim Beatty, associate director of the eProjects program. “It helps transition our students into contributing industry professionals — the engineers of tomorrow — and there is nothing more important than that in today’s world.”

Siemens has amplified the eProjects program by offering students an opportunity to become certified in the company’s industry-grade systems.

“Our software and hardware is used by leading companies of various industries all over the world,” said Mia Fujii, a portfolio development executive for Siemens Digital Industries Software. “Certifying ASU students would give them a leg up when applying for jobs in Arizona’s growing manufacturing industry and beyond.”

Senior design group explores digital twin technology

Engineering majors Jean-Francois Enriquez, Dakota Mathews and Kenneth Alarcon Aguirre chose Siemens as their industry partner for their senior design project partly because of Siemens’ leadership in digitalization technology.

The team excelled in their two-semester project, which was focused on assembling and testing a digital duplicate of an existing physical machine, which is known as digital twin technology. This approach can be used to optimize production line components, process flows and improve throughput.

Using the Internet of Things for replication, digital twins are used in various industries to increase efficiency, advance operations and reduce risk, offering a test bed before application in the real world.

Ryan Klenner, a business development manager for Lightworks, a unit of ASU’s Global Institute of Sustainability and Innovation, views the capstone project experience as a way to amplify the strengths of both students and industry experts and looks forward to how Siemens will use the students’ technology to advance the energy industry.

“Digital twin technology enables humans to do things we weren’t able to do before, opening up a whole new world of possibilities,” Klenner said.

Enriquez, who is now a mechanical systems engineering graduate, says he found the project to be a valuable learning experience. He was recently hired by Siemens as an associate consultant for his exceptional work on this project.

“For months prior, I had only been working on the digital version of this machine, so I remember being so surprised and satisfied when the (physical) machine was running almost exactly how it did on the virtual version,” Enriquez said. “It showed the culmination of months of hard work amounting to that moment and it also showed me, in person, what digital twin technology is all about.”

Fujii says she believes that the reason the project was successful was because the ASU student team was committed to learning new skills and receiving mentorship virtually.

“They completely knocked our socks off with how quickly they learned to design and build a full digital twin using Mechatronics Concept Designer in NX software and Siemens TIA Portal,” she said. “This is not simple stuff, it’s a real application and they not only learned it, they learned it fast!”

The senior design team continued to impress at live presentations to both ASU and Siemens, including an executive-level synopsis of the project and a real-time demonstration of their digital twin in action.

Jerry Gintz, an engineering senior lecturer at The Polytechnic School and the team’s faculty adviser, supported the students as they ventured into new territory.

“The digital twin project was the perfect foundation for students to exploit Industry 4.0 technology to establish a platform for learning and optimizing automated manufacturing processes,” Gintz said. “Ultimately, the project will be replicated to augment hands-on learning for the industrial automation sequence of graduate and undergraduate engineering courses. This project couples nicely with our current educational focus on leveraging technology to help reshore American manufacturing.”

A shared vision prepares students for high-demand industries

In March, ASU was awarded the One Workforce grant, an $8 million grant from the U.S. Department of Labor to lead an initiative that would train workers for high-paying, high-demand jobs in manufacturing, cybersecurity and information technology.

The One Workforce grant will help restore a critical skills shortage in the U.S. by establishing the Arizona Workforce Training Accelerator Partnership for Next Generation Jobs, or AZNext, a program led by various ASU schools including the Fulton Schools and external partners.

“Siemens was one of the companies that provided a letter of support prior to the submission of this proposal, which aligns with ASU’s vision of offering substantial tools to prepare students for the workforce and expanding the manufacturing presence in Arizona,” said Beatty, who leads the eProjects senior design project program. “Their support bolstered our chances of getting the grant.”

Siemens is a member of the AZNext advanced manufacturing advisory board.

“We will continue to invest in ASU and the next generation of engineers,” said Gerald Deren, executive director for academic enablement at Siemens Digital Industries Software. “We believe that today’s engineers need to be ready to tackle the world’s challenges.”

Similarly, the eProjects program will continue to prioritize student preparedness and the program organizers will ramp up its breadth to benefit both students and the manufacturing industry on a broader scale. Enriquez’s example is just one of the many successful academic-to-industry transitions.

He will begin his journey at Siemens by becoming acquainted with the foundational concepts of customer projects. His intensive training introduction will include how-to topics that range from soft skills and customer-facing projects to implementation.

Looking back, Enriquez said, “I believe that the skills I have gained and presented through this project have helped me attain this great opportunity.”

Sona Patel Srinarayana

Communications specialist, Ira A. Fulton Schools of Engineering