22 minute read
RESEARCH
Biology for a Better Tomorrow
– Dean Frank M. LaFerla
Innovation and discovery is what drives the advancement of civilization through continuous improvements in health and the environment. The Ayala School of Biological Sciences strives to encourage an environment of innovation, which is reflected in the impactful research produced annually by our accomplished faculty.
We will continue to investigate the underlying principles of nature, and use the discoveries we make in biology to bring about a better tomorrow.
Concussions Rear Their Head in Unexpected Sport
Concussions in football and soccer have been making headlines, but it turns out another sport also poses a risk. A survey by the Ayala School of Biological Sciences and the School of Medicine shows that injuries are prevalent in water polo, whose high level of physicality hasn’t drawn as much attention. The research revealed information that could help better protect water polo players from this type of traumatic brain injury. In the first of its kind survey, co-directed by James W. Hicks, Ph.D., Professor in the Department of Ecology and Evolutionary Biology and Director of the UCI Exercise Medicine and Sport Sciences Initiative, researchers examined over 1,500 male and female members, former members and associates of USA Water Polo. Those questioned represented a broad level of play, from high school to Masters Club. More than a third said they had sustained a concussion at some point.
Several key findings emerged:
• The majority of head injuries occurred during practice rather than games.
• Goalies were at a disproportionately higher risk of suffering a concussion.
• Women, who represented 40% of the respondents, reported sustaining concussions at greater rates than men.
These details could be used to help better protect players from head injury. For example, since researchers found goalies are especially vulnerable and practice carries more risk than games, coaches could mandate that goalies wear head protection during practice sessions.
More study is needed, the researchers say; the survey participants represent fewer than 4% of the estimated number of water polo players in the U.S. However, this research marks a crucial first step for water polo making the types of rule and equipment changes that other sports have put into place to help protect their players from head injury.
More than a third of water polo players said they had sustained a concussion at some point.
Inflammation’s Red Hot Role in Alzheimer’s Fight
In the battle against Alzheimer’s, inflammation is drawing keen interest. Many scientists believe a deeper understanding of its role could spark groundbreaking approaches for slowing the progression of dementia symptoms or even preventing the disease. Professor Andrea J. Tenner from the Department of Molecular Biology and Biochemistry is among the Ayala School researchers examining inflammation’s impact on Alzheimer’s, for which there is currently no cure.
Studies of brains from Alzheimer’s patients show an overabundance of inflammatory proteins when compared with normal brains. These inflammatory proteins are also overly abundant in many other chronic diseases, including the autoimmune disorders diabetes and rheumatoid arthritis. In addition, scientists have found evidence that people who take anti-inflammatory medications have a reduced risk of developing Alzheimer’s disease. Professor Tenner is on the forefront of the effort to better understand the link between inflammation, the immune system and dementia.
Her research focuses on the complement system, one of the immune system’s many branches. It draws its name from its ability to complement, or enhance, the actions of antibodies. Over 30 proteins comprise the complement system, with two being of special interest: C1q and C5. C1q plays a role in many immune functions, including eliminating cells and cellular debris and producing anti-inflammatory proteins under certain conditions. If the complement system goes to work in response to a bacterial infection or in the brains of people with Alzheimer’s, the protein C5 splits into two parts, C5a and C5b. C5a can bind to and activate immune cells. Professor Tenner’s lab has found that C1q protects neurons – cells in the brain responsible for memory and learning – against initial injury. The team has also discovered that blocking the actions of C5a can reduce the damage caused by Alzheimer’s disease in mouse models. She continues to investigate these relationships and is working on ways to bring new drugs targeting the complement system to clinical trials.
Games, Brains and Emotion: New Findings on Memory
The world is gaining a new understanding of how memories are formed and lost, thanks to researchers at the Ayala School:
3D Games Give a Boost
The impact of environmental enrichment on the hippocampus, which has a role in transferring memory from short to longterm, intrigues Professor Craig E. L. Stark from the Department of Neurobiology and Behavior. He and his colleagues found that playing a complex virtual 3D game worked as a way to stimulate the brain and its learning centers; just playing it for several weeks helped people learn an unrelated memorization task involving that part of the brain. In contrast, playing less complicated 2D games had no impact. These findings could assist in designing engaging mental activities that stimulate our brain, strengthen the capacity to remember, and keep us mentally fit as we age.
Learning from the Brains of the Oldest Old
Memory among the oldest old is a focus of Neurobiology and Behavior and Neurology Professor Claudia H. Kawas, a clinician scientist who is the principle investigator of The 90+ Study. In examining the brains of people without dementia who passed away above the age of 90, the research found 40% had Alzheimer’s disease pathology, even though their memories and cognitive performances had always been normal. Through MRI and PET scans, clinical-pathological investigations and genetic studies, Professor Kawas seeks to better understand this resilience and whether it offers insights for boosting memory among people of all ages.
The Emotional Connection
The link between emotion and memory has drawn the attention of Neurobiology and Behavior Professor and Director of the Center for the Neurobiology of Learning and Memory, Michael A. Yassa. He and his team tested older adults – some whose memory was mildly impaired and others with intact memory. They found the former were more likely than the latter to recall positive emotions, while all participants retained negative memories at about the same rate. Professor Yassa’s laboratory develops new ways to use brain imaging to understand how memory works and how it deteriorates in a number of brain diseases including depression and dementia.
Taking a Lead in Fighting the Addiction Crisis
With skyrocketing opioid abuse bringing new attention to addiction’s consequences, the Ayala School of Biological Sciences has founded a new school center aimed at better understanding and combating the crisis.
Called the Irvine Center for Addiction Neuroscience (ICAN), it draws from UC Irvine’s faculty expertise in basic and clinical research into abuse of opioids and other prescription medications, alcohol, nicotine and stimulants. In bringing together a dynamic group of researchers from 11 departments and four schools, ICAN seeks to tackle the addiction issues facing society today and chart a healthier course for the future.
In addition to research, ICAN will offer addiction neuroscience education and addiction scientific literacy outreach programs. ICAN’s goal is to provide a world-renowned center as well as major university and community resource for addiction research and educational programs. “Currently, very little is understood about the action of drugs of abuse and the progression from recreational use to the development of addiction, as well as the persistent effects of drugs of abuse. These aspects of addiction represent the kinds of major questions the faculty of ICAN will pursue.”
Over the past decade, one key step forward has been demonstrating that addiction is a brain disorder. Substance abuse can cause long-lasting changes in how neurons communicate in what’s called the “reward circuitry.” It involves several regions of the brain, including the ventral tegmental area, or VTA. Rewarding stimuli such as food or sexual pleasure activate the VTA, which sends out information that can affect other interconnected brain regions controlling memory, learning, habit formation and decision-making.
Along with exacting a heavy toll on individuals and families, drug abuse and addiction in the United States cost more than $700 billion a year in increased health care expenses, crime and lost productivity.
ICAN is led by Director Marcelo Wood (Francisco J. Ayala Chair of the Department of Neurobiology and Behavior), Co-Director Frances Leslie (Dean of the Graduate Division) and the Executive Committee (Professors Christie D. Fowler and Steve Mahler from the Department of Neurobiology and Behavior, Catherine Cahill from the Department of Anesthesia and Perioperative Care, and Shahrdad Lotfipour from the Department of Emergency Medicine).
Why I Give
I've spent over 30 years in the medical device industry focused on improving the quality of life of patients worldwide. At the core of this passion was the value of the education and personal development I received at UCI. My loyalty to, and investment in, UCI demonstrates to the next generations of graduates, how important it is to leave a legacy for current students to follow. – Ed L. Chang (B.S. ’84)
Starving Cancer Cells to Death
While great strides have been made in battling cancer, much more work needs to be done. A number of treatments take a harsh toll on the body, and experience is showing that many cancer cells eventually become resistant to most chemotherapy drugs. In fighting this challenge, Ayala School researchers are taking parallel, complementary approaches: focusing on personalized medicine, an approach based on the genetic makeup of individual tumors, or on how to exploit the metabolic changes that are characteristics of all cancers.
Professor Zeba Wunderlich from the Department of Developmental and Cell Biology is studying how cells turn specific genes on and off, a process known as gene expression. Proper control – or regulation – of gene expression is necessary for an organism to develop and function normally. Cancer arises when abnormal genes are turned on, or the genes required for normal development are lost, or both events occur.
Environmental factors such as viruses, chemical toxins and ultraviolet radiation can affect gene expression and turn a normal cell cancerous. Professor Wunderlich’s lab is using state-of-the-art tools to better understand the mechanisms governing this process. The goal is to develop new models showing how slight differences in an individual’s normal genetic makeup affect the way genes are activated.
An obstacle currently confronting personalized medicine is that the majority of tumors contain a mixture of cells whose genetic codes carry different cancer-causing defects. This is why most new treatments targeting individual genes only work for a limited period; some cancer cells within a tumor are almost always impervious to them. Ayala School Professor Aimee L. Edinger, also from the Department of Developmental and Cell Biology, hopes to overcome this obstacle by targeting the growth properties of cancers rather than specific genetic changes.
Cancer cells, which grow continuously due to their mutations, require a steady flow of nutrients to survive. When they can’t feed themselves, they die. Normal cells are different: like bears in winter, they can enter a hibernation-like state when their food supply is low, allowing them to weather short periods of starvation.
Focusing on cancer cells’ dependency on constant nutrients, Professor Edinger has found a way to dramatically reduce prostate tumor growth using a compound that restricts the cells’ ability to acquire nutrition from their environment. Studies with cells in the lab suggest this drug will have the same impact on many other cancers. Her work could eventually help people with many different tumor types, even if it’s not known which malfunctioning genes are causing tumors to grow.
When a Virus Goes Rogue
The term “emerging infection” doesn’t always refer to a new disease. The phrase also pertains to infections that previously had a very low incidence or have gone rogue, suddenly appearing in new places or spreading in a manner not seen before. Capturing much attention these days are emerging infections caused by viral zoonoses, viruses that are transmitted from animals to humans. Zika, now rapidly spreading throughout the Americas, fits into this category.
Zika, originally discovered in rhesus monkeys in the Zika forest of Uganda in the 1940’s, was relatively obscure until the early 2000s. After it was confirmed in Brazil in 2015, the virus and its link to microcephaly in babies made global headlines and sparked understandable public alarm. Since then, the World Health Organization has reported Zika transmission in 45 countries and territories in the Americas. The primary way Zika spreads in the Americas is through the Aedes species of mosquito, which is also found in the United States.
Professor Michael J. Buchmeier from the Department of Molecular Biology and Biochemistry is interested in learning more about the pathogenesis of viruses like Zika. Buchmeier is an expert in viral zoonoses and studies the structure and function of viral proteins and glycoproteins, and the ways the viruses interact with their hosts during persistent infection.
Professor Buchmeier suggests that knowledge learned from past mosquito-driven viral outbreaks may help combat Zika transmission. One of those is yellow fever, which was particularly devastating in the 19th and 20th centuries. When the disease took a toll on workers building the Panama Canal, a program of pesticides, water treatment and water removal was pioneered to fight it by controlling mosquito populations. This has been the foundation for countering mosquito-borne diseases ever since and it has worked well in the U.S. and most of the Americas.
However, the ecological damage caused by wide use of pesticides and the development of resistance to them have prompted research into new strategies, including those based on genetics and molecular biology. Donald Bren Professor Anthony A. James from the Departments of Molecular Biology and Biochemistry and Microbiology and Molecular Genetics has been leading the way. Professor James and his colleagues have used gene-editing technology to generate a new malaria-resistant mosquito. It carries a unique set of genes that produce antibodies against the malaria parasite. Similar technology could also be used to engineer a mosquito that is resistant to Zika.
Can We Predict Death?
A tiny creature could hold answers to the great mystery of mortality. Thanks to the evolutionary links between species, biologists can study the common fruit fly to understand complex species, including our own. Ecology and Evolutionary Biology Professors Laurence D. Mueller and Michael R. Rose have taken this approach to find out if it’s possible to predict the end of life by identifying a process called “the death spiral.
Much is known about fruit flies’ genetics and they have been extensively used to decipher the molecular and genetic biology behind many physiological processes, including aging. Professors Mueller and Rose have studied them over the past two decades to decipher a human phenomenon: Mortality rates increase steadily from young adulthood until the senior years, known as the second phase of life. They level off during the advanced adult ages labeled the third phase. That stage has traditionally been considered the final one, but the work of Professors Mueller and Rose is changing this view.
In examining physiological processes and events that take place during aging, they have discovered that for female flies, a fertility decrease precedes death. This shift occurs faster than other changes and they are pursuing this intriguing discovery in greater depth.
Their findings, along with work on aging issues by other researchers worldwide, have helped shape the case for identifying a fourth phase of life, called “the death spiral.” Referring to an abrupt decline in the body’s functions and systems before an individual dies, it can occur across a range of adult ages and could hold the key to predicting death in an otherwise healthy person.
The BBC and other media have featured this groundbreaking work from Professors Mueller and Rose. As they gain further insights into these changes and the molecular mechanisms involved, their work may reveal ways to better identify individual death spirals or even how to lengthen life by staving them off.
Why I
Give Being involved with the Ayala School of Biological Sciences aligns perfectly with my personal passion for educating and mentoring future generations of healthcare providers.
The School is on the cutting edge of teaching the skills and information students need to succeed in fields from ecology to biology to medicine. I am happy to lend my support through volunteering and philanthropy. – Maria E. Minon, M.D., F.A.A.P. (B.A., B.S. ’72 & M.D. ’76)
Real Dirt on Climate Change
Alaska’s boreal forests have been harboring a secret crucial for the planet’s future and it’s now been revealed by researchers at the Ayala School. Soil fungi have a significant but unheralded role in rising global temperatures, according to Professors Kathleen K. Treseder and Steven D. Allison from the Department of Ecology and Evolutionary Biology. Their work demonstrates that unless climate modelers start paying more attention to fungi, predictions will be inaccurate.
As soil fungi recycle nutrients in dead material from plants and animals, they break down their carbon and release the greenhouse gas carbon dioxide. This process is fairly quick and easy with leaves and other materials freshly left on the Earth’s surface. It’s a longer, more laborious affair with matter buried deeper down, where carbon becomes more stable over time and harder to take apart. Professors Treseder and Allison wanted to find out whether higher temperatures would make soil fungi more active, causing them to increase carbon dioxide emissions by breaking down a greater amount of the more stable carbon.
Contributor: Caitlin Looby, Ph.D. graduate student (not pictured) with Professor Kathleen Treseder. While soil everywhere contains fungi, key factors prompted Professors Treseder and Allison to work with the Alaskan samples. Boreal forests are warming faster than most other ecosystems and their largely untouched landscapes contain vast amounts of stable carbon. Seeking to uncover the molecular mechanisms governing how fungi might change with rising heat, the Ayala School team grew boreal forest fungi in the lab at a variety of temperatures.
Their study showed that the fungi produced special enzymes – small proteins that break carbon apart – that worked best at the temperature in which they were grown. However, the warmer the level of cultivation, the better the enzymes became at breaking down the more stable carbon. These findings suggest that not only do fungi have little problem adapting to higher temperatures – they have the capacity to produce more carbon dioxide emissions and impact on the environment in the process.
Fungi are critical to global carbon regulation, but they have not been getting a lot of consideration in climate models. The work of Professors Treseder and Allison makes a vital case for changing this thinking to improve the accuracy of climate predictions. This in turn could profoundly affect how the world’s governments regulate greenhouse gas emissions.
Why I Give
I love having the opportunity each year to show my support of UCI's Ayala School of Biological Sciences. I want the current class to know that there are alums who understand how vital it is to support them and the unique programs that Bio Sci develops to help train the next group of scientists, doctors and researchers year after year. – Marsha Vacca (B.S. ’71)
Bed Bugs:
Defeating the Enemy You Sleep With
If you think you’ve been hearing more about bed bugs recently, it’s not your imagination. There has been an alarming increase in infestations in the U.S. and throughout the world over the past few decades. At the same time, bed bugs have become resistant to pesticides and there is an urgent need to innovate non-chemical means to combat their spread. Entomologist and Professor Catherine Loudon of the Department of Ecology and Evolutionary Biology is on the forefront of this research.
Bed bugs, small insects that feed on the blood of humans, mainly attack at night while their victims sleep – hence their name. Their bites are often painless at first, but within hours they can turn into itchy welts. Although bed bugs generally do not transmit diseases, they have been an irritating and even painful nuisance for thousands of years.
A common way bed bugs spread and invade your house is by hitching a ride on luggage. Professor Loudon discovered that exposing baggage to temperatures of 165°F for just six minutes will kill the insects. While this approach does not eradicate bugs on the inside, eliminating those on the exterior could be a valuable component of bed bug management, with hotels and airports placing baggage in heating chambers, for example.
The fight against infestations doesn’t stop there. Knowing that heat treatment isn’t the entire answer, Professor Loudon and collaborators recently obtained a patent for an innovative approach that capitalizes on a centuries-known mechanism of trapping bed bugs with bean plant leaves. They have shown that beg bugs become ensnarled in the small, sharp-hooked hairs on the plant leaves, which pierce their feet as they walk over the leaf surface. Once this happens, the bugs can’t get away. Professor Loudon and collaborators plan to develop microfabricated, or synthetic, surfaces that mimic this bed-bug-entrapping action, providing another alternative to chemical treatments.
Take that, bed bugs!
Building a Better Biofuel
In the search to replace fossil fuels with cleaner, more sustainable energy sources, biofuels are receiving considerable attention. There’s a good reason: they are both renewable and energy-dense – delivering a lot of bang for the buck, so to speak.
Biofuels can be synthesized from a range of carbon-rich sources, including gases found in our atmosphere. Professors Markus W. Ribbe and Yilin Hu from the Department of Molecular Biology and Biochemistry have been working on innovative ways to produce renewable biofuels. In recent collaborative work, Professors Ribbe and Hu have discovered that the bacterial enzyme nitrogenase can convert carbon dioxide and carbon monoxide into hydrocarbon energy such as propane. Their findings are unexpected, because previously, nitrogenase was only believed to convert nitrogen to ammonia.
Remarkably, nitrogenase is capable of making hydrocarbons at ambient – or room – temperature and pressure. This would help greatly to reduce cost and potential environmental impact during fuel production. Another benefit: The reaction generates hydrogen as a by-product, which can also serve as renewable energy; some car makers are currently experimenting with hydrogen fuel-cell technology. In addition, making biofuel from nitrogenase could eliminate the use of food crops for this purpose.
Professors Ribbe and Hu have begun establishing a simplified production model, utilizing bacterial cells to make the nitrogenase enzyme and produce biofuels directly. Their work on this endeavor has been published in the prestigious journals Nature Chemical Biology and Nature Communications. Their continued studies will help shape future designs for biofuel production at improved efficiency and reduced cost.
Mankind has been burning fossil fuels as an energy source for over a century. The use of this fuel source has helped create considerable wealth and prosperity, as well as ushered in great innovation, in the western world. However, it has also led to irreversible changes to the planet and must be mitigated for the sake of the environment. At the Ayala School, we recognize that society cannot simply stop using this kind of energy without replacing it with alternative sources. We are proud to be among the researchers worldwide who are working on solving this issue for a better future.
UCI and Tel Aviv University Teaming to Combat Alzheimer’s Around the World
As Alzheimer’s disease soars in the United States, it is also skyrocketing worldwide, making the fight against it an urgent global issue. In partnership with UCI MIND, the Ayala School is now teaming with Tel Aviv University on research, education and training programs to advance this mission. UCI MIND is the UC Irvine Institute for Memory Impairments and Neurological Disorders.
Both institutions have long been committed to the search to better understand and cure the disease. Tel Aviv University’s history of meaningful Alzheimer’s discoveries complements UCI MIND’s advancements in many areas of neurodegenerative research, including treatments, drugs and disease modeling.
The over five million Americans living with Alzheimer’s disease are among an estimated 46.8 million people affected around the world. This global number will reach 74.7 million by 2030, according to Alzheimer’s Disease International, the worldwide federation of Alzheimer’s associations.
