By , February 3, 2022

Scientific breakthroughs are “discoveries that have a major impact on follow-up scientific research.” According to the journal Science, the research breakthrough of the year for 2021 was protein structure predictions. The 2021 People’s Choice award, chosen by Science readers, also placed it at their top-billing. Understanding the structure of hundreds of thousands of proteins offers insights into biological mechanisms and potential to identify new drug targets. Artificial intelligence (AI)-driven software can now predict accurate protein structures for thousands of proteins and their isoforms and complexes of interacting proteins.

Significant research breakthroughs are highlighted annually by Science. Several runners up were also included on their list:

• Ancient soil DNA comes of age are studies of ancient DNA from the soil of cave floors. Nuclear DNA from human and animal occupation of three caves revealed the identity of cave dwellers. Spain’s Estatuas Cave revealed the genetic identity and sex of humans who lived there 80,000 to 113,000 years ago. In Georgia’s Satsurblia Cave, researchers identified a female human genome from an unknown line of Neanderthals, traces of bison, and an extinct wolf. Mexico’s Chiquihuite Cave revealed that the cave bears’ descendants migrated toward Alaska after the last ice age.
• Fusion’s day in the sun refers to fusion reactions that produce energy. The U.S. National Ignition Facility reported a fusion reaction that came close to producing more energy than the laser energy needed to initiate it at a plasma physics conference. Although, significant in-progress materials science and engineering challenges remain before fusion becomes a practical source of energy.
• Potent pills boost COVID-19 arsenal highlights the development of antiviral drugs in preventing symptoms and death if taken early in infection. Some antivirals have received FDA emergency use authorization, and several more are in trials. These drugs are the first line of defense in the absence of vaccines against new strains of viruses or variants of existing viruses.
• Artificial antibodies tame infectious diseases illustrates how monoclonal antibodies (mABs) can regulate immune responses or mark tumor cells for destruction. But few mABs have gained approval for infectious diseases in the United States (limited Ebola, inhalational anthrax, recurrent Clostridium difficile, RSV in high-risk infants, and HIV in people for whom all drugs have failed). The FDA granted emergency use authorization to three SARS-COV-2 mABs for COVID-19 treatment. Work is underway to develop mABs to treat other viral-induced diseases, such as influenza, Zika, RSV, and cytomegalovirus. Advances in cloning and X-ray crystallography make it possible to create and screen many more mABs.
• At last, a crack in particle physics’ standard model describes the muon particle, a heavier, unstable electron cousin. The muon is more magnetic than predicted and gives scientists an indirect way to search for additional, undiscovered particles. Researchers fired a beam of muon particles into a magnetic field, where they twirl like compass needles at a rate that depends on their magnetism. This year, they proved that result was not a fluke.
• CRISPR fixes genes inside the body by reducing a toxic liver protein, transthyretin (TTR) amyloidosis. Six patients received an infusion of tiny fat balls encasing a guide RNA, and the RNA instructions for CRISPR’s genome-snipping enzyme showed signs of disabling the gene. Within four weeks, average blood levels of TTR dropped significantly. Although it will be months before knowing whether this treatment reduced disease symptoms, the data are promising.
• Embryo ‘husbandry’ opens windows into early development by reporting on methods for growing mouse embryos in vitro for 11 days, a week longer than before. The embryos grew organs and sprouted hind legs. Other investigators devised substitutes or made replicas of blastocysts-stage embryos using human embryonic stem cells, induced pluripotent stem (iPS) cells, and even skin cells undergoing a transition to iPS cells. The normal blastocyst implants into the uterus and is the first embryonic stage to feature specialized cells. These substitutes could offer an essential alternative for understanding the initial mechanisms of embryonic differentiation.

The National Institute of General Medical Sciences (NIGMS) states that fundamental science leads to understanding living systems and life processes. The institute emphasizes that “breakthroughs emerge from complex foundations of fundamental knowledge contributed by many people over many years.” Furthermore, “this knowledge leads to better ways to predict, prevent, diagnose, and treat disease,” adding that breakthroughs, “come from unexpected and often surprising areas.” This year’s breakthrough picks by the Science and its readers illustrate NIGMS’s ideas.

Permalink: Protein Structures Lead Breakthroughs in 2021

By , January 3, 2022

December’s Research Matters focused on how Carolina’s research programs have persevered during the pandemic. Several accomplishments were highlighted that related to Initiative 4: Discover of the university’s strategic plan, Carolina Next: Innovations for Public Good. None of these accomplishments would have been achieved without the incredible effort of staff to ensure that our research operations continued.

On the heels of the significant disruptions of 2020, followed by unique challenges of 2021, and now a looming threat of yet another Sars-CoV-2 variant at the start of 2022, our research support offices have remained operational through it all. We know that the fluid nature of the pandemic is personally taxing, and we are so appreciative that our workforce has remained dedicated through all these trials.

Although certainly not an exhaustive list, the examples highlighted below capture the essence of the incredible work our research support offices accomplished this past year:

• The Office of Clinical Trials (OCT) and the Office of Research Information Systems launched the OnCore clinical trials management system. They began expanding the systems to units beyond Lineberger Comprehensive Cancer Center. OCT also launched the new Billing Coverage Analysis
• The OVCR Research Administration Service Center expanded to serve more units. The Office of Sponsored Research launched its updated Subrecipient Initiation Portal and continued to expand the Carolina Rapids training program for the campus. OSR also negotiated a rate extension for our F&A return, keeping it at the critical 55.5% level.
• The Office of Animal Care and Use and the Division of Comparative Medicine successfully achieved reaccreditation from AAALAC and a flawless inspection by the USDA. This accomplishment is unique for institutions across the country as complex as Carolina and was achieved by hard work and concern for the care of animals.
• The Office of Human Research Ethics successfully supported the campus COVID-19 research efforts, where they saw a 33% increase in the number of IRB submissions during 2021.
• The Office of Research Development (ORD) celebrated the success of the Creativity Hubs program, which continued its supports of innovative new research such as:
  • chemical and molecular designs that desalinate and capture heavy metals from water;
  • data collection and integration of extreme storms and flooding to aid in predicting impacts of future storms on coastal habitats and their inhabitants;
  • discovery and development of antiviral therapeutics using new methods targeting a person’s cellular machinery; and
  • use of AI technology to identify novel matter for solar fuels and develop robotics to automate chemical synthesis and characterization.
• ORD also supported large grant proposals through team building, project management, and grant writing support. They led a substantial increase in the total number of limited submissions from federal and private sponsors and supported several key collaborative efforts in arts and humanities.
• The Office of Postdoctoral Affairs provided career counseling for postdoctoral fellows affiliated with over 50 departments. The Carolina Postdoctoral Program for Faculty Diversity successfully recruits talented, diverse researchers to the Carolina faculty. For the 2021 cohort, scholars have accepted faculty positions at Carolina in history, health behavior, and in the schools of Nursing and Government.
• The OVCR managed the Pinnacle Hill collaboration with Deerfield to develop therapeutics for commercial interests. Another avenue for corporate sponsorship opportunities, the Advance Therapeutics Initiative (AdvanTx) is advancing the discovery and development of therapeutics at UNC.
• The Office of Partnerships and Research Impact worked with North Carolina’s Office of Strategic Partnerships, facilitating new pathways for centers and institutes to engage with state agencies and provide those agencies with expertise to better serve the people of the state.
• The Office of Research Communications coalesced stories, messaging, and branding for the OVCR around the phrase” “Research Perseveres,” highlighting perseverance at the bench, in the field, in the classroom, and in the offices that support research infrastructure. They also led this year’s University Research Week, which was the largest and most successful iteration of that event yet, with over 66 events and nearly 3,000 participants. Perseverance was also highlighted in this year’s Endeavors The magazine is an incredible showcase of tenacity and persistence of researchers at all stages and across many different disciplines.

Research at Carolina is at the most successful place it has ever been. While there is much to celebrate on that front, we know that this growth requires great effort from UNC’s research support offices. The work of those that support the research mission has not gone unnoticed. Their contributions are meaningful, essential, and truly matter to the university, the state, and citizens of North Carolina.

As we look to the new year, the take-away message is one of optimism. We have a new state budget for the first time in three years. We have had another record-breaking year for research awards, which subsequently puts us on track for continued success. Although we do face challenges, overall, the university research support infrastructure is outstanding. We will mitigate challenges as quickly as possible, and we will continue to look for ways to provide the resources needed to equip these offices.

2022 will be a better year, and I look forward to working alongside our staff as we continue to provide our world-class researchers world-class support.

Permalink: World-Class Support for World-Class Researchers

By , December 1, 2021

As 2021 comes to an end, Associate Vice Chancellor for Research Joyce Tan and I want to reflect on progress of Initiative 4: Discover, the research framework for the University’s strategic plan Carolina Next: Innovations for Public Good. Discover is one of eight initiatives representing core areas of focus and targeted investments by UNC.

Carolina Next is not a comprehensive list of university priorities. Rather, it is a document that evolves as new opportunities and challenges present themselves. The connection among Discover, Serve to Benefit Society (initiative 6) and Globalize (initiative 7) became abundantly clear as work during the year showed how Carolina’s research not only enhances the scholarly mission, but impacts innovation throughout North Carolina and the world beyond.

The Gillings School of Public Health and the School of Medicine’s Marsico Lung Institute collaborated this year to demonstrate how an oral antiviral drug for treatment of COVID-19 blocked virus transmission and reduced lung damage. The School of Medicine and the Institute for Global Health and Infectious Disease led a Phase 2 clinical trial of molnupravir and the results led industry partners Merck and Ridgeback Biotherapeutics to seek emergency-use authorization.

The Rapidly Emerging Antiviral Drug Development Initiative, READDI, grew out of the Infectious Disease Drug Discovery Program Creativity Hub. READDI is developing a global partnership among academia, industry, and foundations to develop antiviral drugs against future emerging pandemics. The focus is to study the host cellular impact of antiviral families most likely to cause a pandemic by developing therapeutics that target the viruses themselves, as well as highly conserved host proteins needed for viral replication.

The Lineberger Comprehensive Cancer Center has developed a personalized immunotherapy program for therapies that modulate a cancer patient’s immune system. The patient’s immune cells are removed, manipulated in vitro, and then placed back into the patient to target and kill cancer cells. This treatment protocol requires a specialized Good Manufacturing Process facility, which Lineberger has constructed. Several active clinical trials are ongoing.

Research for service and policy is a key component of Discover. Jonas Monast in the Law School collaborated with the Institute for the Environment on a report based on a year-long project analyzing our state’s policy options to decarbonize the electricity sector. The NC State Environmental Management Commission relied on the report to shape new policy. This work also has potential for global impact as illustrated by policies discussed at the November Glasgow COP26 climate conference.

Center for Health Promotion and Disease Prevention Director Alice Ammerman and the Sheps Center’s Seth Berkowitz and Darren DeWalt joined with Blue Cross NC to address food insecurity through better nutrition. The study is addressing health outcomes through non-medical drivers of health, namely food, and the results have global implications for using nutrition to treat chronic conditions.

To promote artistic and humanist teams, the Office of Research Development identified a funding opportunity focused on music therapy sponsored by the NIH Institute of Integrative and Complementary Medicine. The College of Arts & Sciences partnered with the School of Medicine’s Department of Allied Health Sciences and clinical and Appalachian State University’s music therapy program. They’re currently concepting a rehabilitative breathing program for long COVID patients using operatic breathing techniques.

Our office also partnered with the Institute of Arts and Humanities to encourage artistic practice by providing pilot grants. Examples of such work include Mohamed Mwamzandi’s digitization of Pulaar Islamic texts in Senegal and Mali to preserve a vital language from extinction. Angela Stuesse’s research on immigration policy, homophobia, racism, and family separation impacts on the life experience of an undocumented youth was also funded by this program. Her studies blend ethnography and cultural analysis to cultivate empathy and understanding.

Research Perseveres was the theme for this year’s University Research Week, which was held last month. The theme was chosen to illustrate how research at Carolina progressed during the challenges of the pandemic, civil rights protests, and other unprecedented events of the last year. Amongst the more than 60 events featured during the week, the signature event — The Health of Our State and Beyond series — highlighted winning Creativity Hubs teams who provided overviews of the challenges they are working to eradicate around the world, despite the pandemic.

UNC’s research and innovation pipeline came together with the official launch of the Institute for Convergent Science (ICS) this year. While research encompasses fundamental investigation, discovery, and pre-development, the ICS covers the pre-commercial environment with technical and product de-risking and development. Along with Innovate Carolina, this pipeline establishes a comprehensive innovation ecosystem supported by the Advance Therapeutics Initiative (AdvanTx) — which brings together scientific expertise to organize and advocate for funding to develop a commercialization strategy. Currently, the AdvanTx team has vetted more than 30 projects and is actively working to advance several more.

UNC’s gene therapy investments have propelled Research Triangle Park as a go-to place for corporate expansion of gene therapy manufacturing. The NC VVIRAL project represents an academic-industrial partnership focused on developing next-generation biomanufacturing processes for gene therapy products and the development of tailored curricula to train the biomanufacturing workforce.

These examples are just a few of many scholarly advances that have been made this year. Many more stories can be found in Endeavors, which is the publication that showcases Carolina’s best science and artistic discovery. Three series within the Endeavors publication include:

• Foundations, which uncovers the nature of basic science and its potential to shape the world;
• Research Uncovered, a biweekly series that showcases researchers at all career levels and highlights what inspires them, how they overcome obstacles, and a little about their lives outside labs and offices; and
• Time & Tenacity, which focuses on Carolina discoveries and inventions since the founding of the university.

I’d like to emphasize again that Carolina Next is a living and dynamic process. Under the Discover initiative, we are continuously planning, evaluating, and changing to meet the problems of the day. This process involves the OVCR interacting biweekly with UNC’s research deans and pan-campus centers and institutes directors. This group is now diving into research at the College, the schools, and our centers and institutes to create individual strategic plans that guide the Discover objectives.

Research has persevered at Carolina during the challenges of the last few years thanks to the dedication of our faculty, staff, and trainees. Our research enterprise is one of the best in the country — one that we can take pride in.

Permalink: Carolina’s Research Perseveres through the Pandemic — and Beyond

By , November 3, 2021

Last monthʼs Research Matters focused on the benefits of international scientific collaboration. Collaboration incentivizes open science, which is a topic of interest in the research community today. One definition of open science is “the idea that scientific knowledge of all kinds should be openly shared as early as is practical in the discovery process.” The National Academies of Science, Engineering, and Medicine slightly expands that definition to reflect that open science is “an effort that aims to ensure the free availability and usability of scholarly publications, the data that result from scholarly research, and the methodologies, including code or algorithms that were used to generate those data.”

The Pew Research Center survey conducted in 2019 found that U.S. adults trust scientific research findings more if researchers make their data publicly available, which allows for independent review and corroboration.

One particularly potent example of publicly available data is The Cancer Genome Atlas , a landmark open-science program that characterized over 20,000 primary cancer and matched normal samples spanning 33 cancer types. This remarkable program was a joint effort between the National Cancer Institute and the National Human Genome Research Institute that brought together international researchers from diverse disciplines and multiple institutions. The program has a Genomic Data Commons Portal, which harmonizes cancer datasets available to the research community worldwide. In addition, investigators developed computational tools for data analysis and the technologies utilized to generate data that are available to everyone.

Another amazing example of open science is the NIH All of Us research program. The program is recruiting one million people across the U.S. to build a diverse health database for researchers to learn how biology, lifestyle, and environment affect health. The All of Us Research Hub allows investigators to view data and methods of data curation and access a workbench platform with a suite of custom tools.

The Open Research Area was established to strengthen international co-operation in the social sciences. It is a joint agreement between France, Germany, the United Kingdom, and the Netherlands to promote international collaboration, improve coordination between teams of researchers from different European states, and enable research collaboration with major and emerging research nations beyond Europe.

The Open Library of Humanities facilitates the open-access publication of all humanities disciplines. This international consortium of libraries funds open access publication of scholarly work with no author-facing article processing charges.

The UNC Health Sciences Library has an Open Access and Scholarly Communications portal that defines open access as “free, online availability of scholarly content that is free from most copyright and licensing restrictions.” This portal is an important guide for faculty to navigate open access publishing.

Examples like these inspired the National Academies to establish a roundtable forum focused on aligning incentives for open science. The roundtable has been convening two times per year exchanging ideas and strategies amongst stakeholders, including universities, funding agencies, societies, philanthropies, and industry.

In 2020, the forum held a workshop called Developing a Toolkit for Fostering Open Science Practices. One goal of the workshop was to reimagine the credit and reward systems for academic appointments, tenure, and promotion (APT) and grants in a manner that would incentivize open science practices. The workshop emphasized how academic research environments previously incentivized competition between individual researchers for hiring and promotion.

The increasing technical sophistication of research and the use of data in all disciplines makes it impossible for a single individual or lab to work alone. Success requires teams of researchers with diverse knowledge and skills to facilitate ongoing discovery, which means the APT process in academia is changing to account for scholarly contribution rather than order of authorship. Iʼm encouraged that Carolinaʼs recently revised APT guidelines align with collaborative and open research.

Permalink: Open Science Fuels Collaboration