| THE FUTURE OF AGING |
Although people often worry about their memory as they get older, aging is not all downhill.
Alan Castel in the Department of Psychology has found that despite some memory decline, many healthy older adults can selectively remember important information, such as remembering to take medications or pack a passport for a trip. And older adults can improve their mood by choosing to focus on positive emotional events. In addition, wisdom and creativity can blossom in older age, allowing people to come up with novel and innovative solutions to all kinds of problems. Castel’s research shows that curiosity allows the mature brain to focus on what is interesting, leading to memory benefits for what we find most important in life. With more new insights into about how memory works, he plans to improve and develop new strategies and selective attention techniques so that people can remember what is most important (and choose to forget the rest!).
Meanwhile, the common fruit fly is helping unlock one of the secrets of the fountain of youth.
David Walker in the Department of Integrative Biology and Physiology uses the genetics of the insect to better understand the molecular and cellular mechanisms that cause age-related deterioration. In a study on middle-aged fruit flies, Walker and colleagues developed a “cellular time machine” that helps to remove toxic, damaged mitochondria from aged cells. The approach focuses on mitochondria, the tiny power generators within cells that control the cells’ energy levels and determine when they live and die. Mitochondria often become damaged as people age, accumulating in the brain, muscles and other organs. When cells can’t eliminate the damaged mitochondria, those mitochondria can become toxic and contribute to a range of age-related diseases. Walker’s research could lead to drugs that delay the onset and progression of human age-related diseases such as Parkinson’s, Alzheimer’s, cancer, stroke and cardiovascular disease.
| THE FUTURE OF BIODIVERSITY |
Many of the fruits and vegetables we eat come from plants and crops that depend on bees for pollination, an example of nature’s interdependence that is vital to ecosystem health and stability.
Luke Nikolov of the Department of Molecular, Cell and Developmental Biology is working to understand the developmental basis of nectar, a key factor in plant pollination. Plants display an elaborate array of color, form and scent to attract bees, but the sugary liquid is the ultimate reward. Plants produce nectar in secretory structures called nectaries. Using the latest gene editing technology, Nikolov and his students are identifying genes that control how and where the nectaries are built, and the mechanisms responsible for nectar formation and secretion. These findings will provide insights essential to agriculture and bee health, and could lead to new approaches to increase crop yield.
Modern civilization is molding life on Earth at an unprecedented scale and speed.
Shane Campbell-Staton in the Department of Ecology and Evolutionary Biology and his collaborators are studying the effects of civil conflict on the evolution of elephants in southern Africa. In the wake of the 15-year civil war in Mozambique, more than 90 percent of large mammals in some regions were killed. The elephant population in Gorongosa plummeted from thousands to mere hundreds as they were hunted for food and ivory. Of the female elephants who survived, half lacked their trademark tusks — a much higher number of tuskless females than normal. Using genome sequencing and studies of tooth development, Campbell-Staton is searching for the genes responsible for tusk loss. Researchers are also deploying various tracking technologies and field observations to understand whether the loss of such a versatile tool may fundamentally impact the landscape and other species. Understanding such cascading impacts of conflict will inform conservation efforts as the Gorongosa ecosystem recovers from the war.
From overfishing to coral bleaching and ocean plastics, many marine threats have been detected too late to prevent lasting damage.
Paul Barber of the Department of Ecology and Evolutionary Biology and his students are helping revolutionize how we monitor changes to marine biodiversity caused by pollution and climate change. In the coral reefs of Indonesia, Barber and his collaborators place stacks of 12-inch plastic plates, which become colonized by everything from bacteria and bryozoans to corals and crabs. They then extract and sequence the DNA of these organisms to reconstruct complex marine communities in the search for individual species that are early harbingers of environmental change. Along the California coast, Barber and his students are also reconstructing entire marine communities — but from just a few liters of seawater. This is possible because all marine animals, from humpback whales to garibaldi fish, leave behind DNA traces that can be extracted and sequenced to monitor local changes in marine ecosystems. This work is providing marine resource managers new tools to promote sustainability of imperiled marine ecosystems.
| THE FUTURE OF BRAIN HEALTH |
Post-traumatic stress disorder (PTSD) is rife in communities that are disproportionately plagued by conflict and violence.
Lauren Ng in the Department of Psychology researches the effectiveness of PTSD interventions in these locations, focusing on how individual, cultural and contextual differences influence treatment effectiveness for diverse patient populations. Although more than 80 percent of the world’s population lives in low-and middle-income countries (LMICs), little of the research on treatments for mental disorders, including PTSD, has originated in those countries. Many current treatments have been developed and tested in fully resourced academic settings and do not translate well to under-resourced LMICs or rural American communities. Ng aims to increase access to treatment and reduce health disparities for communities previously overlooked in PTSD research. This will lead to innovative treatments and models of care — potentially delivered by peers, community members, lay providers and/or primary care providers — that are culturally grounded and available to all.
Current treatments for addiction are only modestly effective, and not all patients respond to them the same way.
Lara Ray in the Department of Psychology is developing more effective tailored treatment options to combat addiction using a clinical research approach that combines brain imaging, pharmacology and genetics. Her lab is conducting large-scale clinical trials to improve treatments for alcoholism and smoking cessation. In earlier studies, she found that genetic variation may predispose certain individuals to a more“rewarding” response to alcohol when they drink, and that these drinkers respond favorably to a medication that blocks the rewarding effects of alcohol. Ray has also found that smokers who drink heavily are much more likely to lapse into smoking during a drinking episode. To curb the effects of alcohol on smoking urges, she has found that using a combination of medications for drinking and smoking is more effective than either medication alone, and superior to placebo.
Depression will soon be the leading cause of global disease burden, afflicting 300 million people worldwide. Less than half of individuals receive treatment, and relapse is not uncommon.
Capitalizing on the latest advances in neuroscience and technology, Michelle Craske in the Department of Psychology is developing new treatments for anxiety and depression. She recently developed a new treatment for anhedonia, the inability to anticipate or experience pleasure, which is a symptom of anxiety and depression associated with high suicide risk. The treatment, which teaches skills of anticipating, savoring and learning reward, has been shown to be more effective than standard psychological treatment. Next up is a thorough exploration of the neural mechanisms of this treatment, i.e., exactly how it works. Craske also leads the Innovative Treatment Network for the UCLA Depression Grand Challenge, which provides screening, tracking and treatment for depression and anxiety for UCLA students via smartphones, combined with in-person treatment for those in greatest need.
| THE FUTURE OF DISEASE |
Stem cell gene therapy offers new hope for treatments – and even cures – for a range of genetic conditions.
Donald Kohn in the Department of Microbiology, Immunology and Molecular Genetics is testing novel approaches to treating genetic diseases such as Sickle Cell Disease (SCD) and Severe Combined Immune Deficiency (SCID), also known as “bubble baby disease.” In these diseases, an inherited mutation in a single gene causes blood cells in bone marrow to malfunction. Today, more than 40 SCID babies are living infection-free thanks to a new approach developed in Kohn’s lab that doesn’t rely on a perfectly matched stem cell donor. Instead, the patient’s own stem cells are extracted, a normal copy of the relevant gene is added, or that gene is fixed, and these are transplanted back to the patient. These “self” transplants are safer since the patient’s cells are a perfect match. Based on the success of the SCID trial, a clinical trial for SCD will begin soon.
The word “pandemic” conjures up fears of disease, contagion and global catastrophe, from the Black Death to HIV/AIDS to Ebola.
Jamie Lloyd-Smith in the Department of Ecology and Evolutionary Biology studies the conditions in which deadly viruses circulating in animal populations, such as avian influenza and Nipah, a bat-borne virus, can cross over and cause human pandemics. He builds mathematical and computer models, and integrates ideas and data across disciplines, from molecular biology to climate change. The result is new understanding of how ecological dynamics in wildlife populations, evolutionary pressures on pathogens, and changes in human societies can combine to form the conditions for pandemics. He recently discovered that we’re all already protected against some avian influenza strains, with immunity that varies depending on our birth year and the first seasonal flu strain we caught. Lloyd-Smith’s work is providing new tools to prioritize pandemic threats, so we can spot the next big one before it strikes and take action to prevent it.
Autism and other neurological disorders are poorly understood.
This could soon change, thanks to Xinshu (Grace) Xiao in the Department of Integrative Biology and Physiology, who researches RNA abnormalities. While DNA contains the instructions for life, RNA acts as a messenger that carries out these instructions and plays essential roles in health. The same piece of DNA can generate multiple versions of RNA through transcription and RNA processing, possibly leading to different protein sequences. Xiao and her collaborators recently discovered differences in the brains of autism patients involving RNA editing, in which genetic material is normal, but modifications in RNA alter nucleotides. The study identified two proteins, FMRP and FXR1P, which regulate abnormal RNA editing in autism. FMRP is known to be a critical protein to autism pathogenesis, and mutations in FMRP cause Fragile-X syndrome, a disorder closely related to autism. Xiao hopes to reveal new insights into autism mechanisms and causes, which could lead to new treatments for this and other neurological disorders.
Current cancer therapies are often ineffective, toxic to the patient, and do not prevent relapse. Immunotherapy has shown great promise as part of a new generation of cancer medicine.
Lili Yang in the Department of Microbiology, Immunology and Molecular Genetics is developing novel immunotherapies to fight cancer with the body’s own immune cells, specifically invariant natural killer T (iNKT) cells. Our immune system comprises a small, powerful network of blood cells that survey, detect and destroy harmful invasions by germs or viruses. Some cancers can evade immune system detection because it’s the body’s own cells that have turned malignant through rapid, uncontrolled division. Yang aims to develop gene therapies that engineer patient immune systems to recognize and kill cancer cells while leaving healthy tissue unharmed. If clinical trials with iNKT cells are successful, it has the potential to become a general immunotherapy for treating multiple cancers.
| THE FUTURE OF MICROBIOME RESEARCH |
Little is known about the trillions of native intestinal microorganisms inhabiting our bodies, collectively called gut microbiota.
Elaine Hsiao in the Department of Integrative Biology and Physiology studies interactions among the microbiome, brain and behavior, and their potential links to neurological disorders such as autism, depression and Parkinson’s, as well as social, communicative, emotional and anxiety-like behaviors. She focuses on specific microbes that regulate neurochemicals; influence immune cells in the brain; and interact with environmental factors, such as diet, medications and stress, which can predispose people to neurological diseases. Hsiao demonstrated strong links between changes in gut microbiota and changes in behaviors relevant to anxiety, depression and autism. She also identified specific gut bacteria that play an essential role in the anti-seizure effects of a high-fat, low-carbohydrate ketogenic diet and was the first to establish a causal link between seizure susceptibility and gut microbiota. Hsiao’s research could reveal new treatments for neurological and neurodevelopmental diseases.
With up to a billion new mutations of microbes entering our gut microbiome daily, bacterial genomes inside the body can evolve rapidly. This is both an opportunity (e.g., enabling digestion of new foods) and a challenge (e.g., the evolution of drug resistance).
Nandita Garud in the Department of Ecology and Evolutionary Biology uses population genetics to understand how human gut microbiome evolves. Garud and her collaborators recently quantified the evolutionary dynamics of roughly 40 prevalent species of gut bacteria. They found that gut bacteria can evolve in humans in the space of just six months, but that over our lifetimes, the bacteria inside us are completely replaced. These results suggest that gut bacteria can evolve on time scales relevant to our health, but that they do not become so personalized that they cannot be replaced. This work could pave the way for a range of therapeutic applications, including predicting antibiotic drug resistance in gut microbiota and developing fecal microbiome transplants that can effectively cure diseases.
