Our innovation and catalyst awards support creative and bold proposals to generate paradigm-shifting insights into the biology of brain aging, the drivers of neurodegenerative disease and opportunities to promote brain health and resilience long into what we now consider "old age".
Innovation grant projects
Mechanistic dissection and therapeutic capture of an exercise-inducible metabolite signaling pathway for brain resilience
Exercise improves cognition and protects against age-associated neurodegenerative diseases, but further research is needed to understand exactly how this occurs. This project aims to pave the way for therapeutics that can capture the benefits of exercise for promoting brain resilience.
Manipulating inflammation in the aging brain to promote brain resilience
Inflammation is a hallmark of brain aging, yet the source of inflammation in the old brain — and how to eliminate it — is unknown. This team aims to provide insight on how inflammation affects the aging brain that could potentially lead to the generation of new therapies to promote brain resilience.
Role of Proteostasis and Organelle Homeostasis in Brain Resilience during Aging
This team aims to define how and why protein production breaks down in aging cells, leading to disease. This research may lead to new diagnostic and therapeutic approaches against neurodegenerative diseases and potentially aging itself.
Unleashing engineered T cells as disease sensors and therapeutic actuators for neurodegenerative disease
This project will explore whether amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) result from immune cells attacking altered neurons. The team aims to pioneer the use of engineered immune cells as therapies for neurodegenerative disorders.
From gut to brain: reprogramming peripheral macrophages at the intestinal barrier to prevent age-associated inflammation and cognitive decline
This team will investigate whether a decline in intestinal immune cell metabolism drives age-related inflammation and cognitive decline. By replacing aged intestinal macrophages with metabolically healthy ones, they hope to develop a novel approach to enhance cognitive resilience.
Mutant microglia and resilience to Alzheimer’s disease
This project aims to identify how mutant peripheral immune cells that invade the brain might actually reduce Alzheimer’s disease risk. The research will explore how to mimic these cells’ resilience-promoting effects to design new Alzheimer’s therapies.
Catalyst grant projects
Mitochondrial DNA and Brain Resilience
This team proposes the first comprehensive study of how mitochondrial DNA is related to cognitive function and susceptibility to dementia in a diverse population of over 11,000 adults. The outcomes of this study will provide insight into possible racial disparities in brain health.
Characterizing the Genetic Architecture of Neuropathology with Machine Learning
This team will study the brains of individuals who lived past ninety with their cognitive function intact, using advanced tissue imaging and computer science to understand mechanisms of resilience that could slow neurodegeneration and preserve brain health.
Preserving motor engrams in Parkinson's disease: Neural circuit and transcriptomic studies and strategies for resilient motor control
This team aims to better understand how Parkinson's disease attacks the brain's basic motor programs and to spawn novel therapies against the disease using gene-editing technology.
Endocannabinoid metabolism as a driver of brain aging
This team aims to discover whether the brain’s endocannabinoid system is dysregulated during aging, triggering inflammation via molecules called prostaglandins. If so, a drug that decouples these systems might restore a youthful brain state and rescue cognitive function.
Resilience to Synaptic Impairments in Neurodegenerative Disorders
This team will explore the idea that neurotoxic protein aggregates seen in neurodegenerative disorders act at the synaptic connections between cells, and that resilience against these disorders may come from natural synapse-supporting factors that could be transformed into new forms of therapy.
Unlocking brain resilience with HDAC inhibition
This team aims to define a network of genes that contribute to stress resistance in neurons and identify how it could be activated to enhance brain resilience and protect against neurodegenerative disease.
Predicting and promoting resilient brain aging trajectories
Using new animal models such as the African killifish, this team aims to develop approaches to predict individual brain aging trajectories early in life based on behaviors that can be modulated to promote healthy memory, executive function and processing speed as well as counter dementia.
Defining the Subcellular Biology of Brain Aging and Neurodegeneration
This team plans to map how age-related dysfunction of cellular waste disposal in lysosomes could lead to neurodegenerative diseases, potentially laying the foundation for a map of organelle function in the brain.
Investigating severe traumatic brain injury using a novel human CSF cell-free mRNA gene panel
This team aims to be the first to study the cellular and molecular impact of traumatic brain injury by studying genetic material in human cerebrospinal fluid. This will help clinicians and researchers ID markers of brain resilience after injury, and ultimately improve treatment for severe TBI.
Sleep circuits in neurodegenerative disease and aging
This team plans to study whether changes in neurons in the midbrain that regulate sleep, wakefulness, and immunity could contribute to aging and neurodegeneration. If successful, this information could rescue deficits in sleep and restore a normal immune profile.