The field of human biology faces three major technological challenges. Firstly, the causation problem is difficult to address in humans compared to model animals. Secondly, the complexity problem arises due to the lack of a comprehensive cell atlas for the human body, despite its cellular composition. Lastly, the heterogeneity problem arises from significant variations in both genetic and environmental factors among individuals. To tackle these challenges, we have developed innovative approaches. These include 1) mammalian next-generation genetics, such as Triple CRISPR for knockout (KO) mice and ES mice for knock-in (KI) mice, which enables causation studies without traditional breeding methods; 2) whole-body/brain cell profiling techniques, such as CUBIC, to unravel the complexity of cellular composition; and 3) accurate and user-friendly technologies for measuring sleep and awake states, exemplified by ACCEL, to facilitate the monitoring of fundamental brain states in real-world settings and thus address heterogeneity in human.

Over the course of evolution, the human race has achieved a number of remarkable innovations, that have enabled us to adapt to and benefit from the environment ever more effectively. The ongoing environmental threats and health disasters of our world have now made it crucial to understand the cognitive mechanisms behind innovative behaviours. In my talk, I will present two research projects with examples of innovation-based behavioural adaptation from the taxonomic kingdom of animals, serving as a comparative psychological model for mapping the evolution of innovation. The first project focuses on the challenge of overcoming physical disability. In this study, we investigated an injured kea (Nestor notabilis) that exhibits an efficient, intentional, and innovative tool-use behaviour to compensate his disability, showing evidence for innovation-based adaptation to a physical disability in a non-human species. The second project focuses on the evolution of fire use from a cognitive perspective. Fire has been one of the most dominant ecological forces in human evolution; however, it is still unknown what capabilities and environmental factors could have led to the emergence of fire use. In the core study of this project, we investigated a captive population of Japanese macaques (Macaca fuscata) that has been regularly exposed to campfires during the cold winter months for over 60 years. Our results suggest that macaques are able to take advantage of the positive effects of fire while avoiding the dangers of flames and hot ashes, and exhibit calm behaviour around the bonfire. In addition, I will present a research proposal targeting the foraging behaviour of predatory birds in parts of Australia frequently affected by bushfires. Anecdotal reports suggest that some birds use burning sticks to spread the flames, a behaviour that has not been scientifically observed and evaluated. In summary, the two projects explore innovative behaviours along three different species groups, three different habitats, and three different ecological drivers, providing insights into the cognitive and behavioural mechanisms of adaptation through innovation.

Parkinson’s Disease (PD), the most common neurodegenerative movement disorder, is based on a complex interplay between genetic predispositions, aging processes, and environmental influences. In order to better understand the gene-environment axis in PD, we pursue a multi-omics approach to comprehensively interrogate genome-wide changes in histone modifications, DNA methylation, and hydroxymethylation, accompanied by transcriptomic profiling in cell and animal models of PD as well as large patient cohorts. Furthermore, we assess the plasticity of epigenomic modifications under influence of environmental factors using longitudinal cohorts of sporadic PD cases as well as mouse models exposed to specific environmental factors. Here, we present gene expression changes in PD mouse models in context of aging as well as environmental enrichment and high-fat diet.

Obesity and neurodegeneration lead to millions of premature deaths each year and lack broadly effective treatments. Obesity is largely caused by the abnormal function of cell populations in the hypothalamus that regulate appetite. We have developed methods generate human hypothalamic neurons from hPSCs to study how they respond to nutrients and hormones (e.g. leptin) and how disease-associated mutations alter their function. Since human hypothalamic neurons can be produced in large numbers, are functionally responsive, have a human genome that can be readily edited, and are in culture environment that can be readily controlled, there is an unprecedented opportunity to study the genetic and environmental factors underlying obesity. In addition, we are fascinated by the fact that mid-life obesity is a risk factor for dementia later in life, and caloric restriction, exercise, and certain anti-obesity drugs are neuroprotective, suggesting that there are shared mechanisms between obesity and neurodegeneration. Studies of HPSC-derived hypothalamic neurons may help bridge the mechanistic gulf between human genetic data and organismic phenotypes, revealing new therapeutic targets. ​

Interval timing is a fundamental component action, and is susceptible to motor-related temporal distortions. Previous studies have shown that movement biases temporal estimates, but have primarily considered self-modulated movement only. However, real-world encounters often include situations in which movement is restricted or perturbed by environmental factors. In the following experiments, we introduced viscous movement environments to externally modulate movement and investigated the resulting effects on temporal perception. In two separate tasks, participants timed auditory intervals while moving a robotic arm that randomly applied four levels of viscosity. Results demonstrated that higher viscosity led to shorter perceived durations. Using a drift-diffusion model and a Bayesian observer model, we confirmed these biasing effects arose from perceptual mechanisms, instead of biases in decision making. These findings suggest that environmental perturbations are an important factor in movement-related temporal distortions, and enhance the current understanding of the interactions of motor activity and cognitive processes. https://www.biorxiv.org/content/10.1101/2020.10.26.355396v1

The human cortical ribbon varies during the lifespan, from childhood to senescence. To study the effects of genetic and environmental factors on these dynamics, one needs to measure specific phenotypes (cortical volume, surface area, thickness, new neuroimaging phenotypes such as intracortical myelination or multimodal ones based on their combination, or their asymmetries) that characterize the cerebral grey matter accurately

Learning by analogy is a powerful tool children’s developmental repertoire, as well as in educational contexts such as mathematics, where the key knowledge base involves building flexible schemas. However, noticing and learning from analogies develops over time and is cognitively resource intensive. I review studies that provide insight into the relationship between mechanisms driving children’s developing analogy skills, highlighting environmental inputs (parent talk and prior experiences priming attention to relations) and neuro-cognitive factors (Executive Functions and brain injury). I then note implications for mathematics learning, reviewing experimental findings that show analogy can improve learning, but also that both individual differences in EFs and environmental factors that reduce available EFs such as performance pressure can predict student learning.

Dementia is of global interest because of the rapid increase in both the number of individuals affected and the population at risk. It is essential that the risk factors be carefully delineated for the formulation of preventive strategies. Epigenetics refers to external modifications that turn genes "on" or "off”, and cross-cultural studies of migrant populations provide information on the interplay of environmental factors on genetic predisposition. The Indianapolis-Ibadan Dementia Study compared the prevalence, incidence and risk factors of dementia in African Americans and Yoruba to tease out the role of epigenetics in dementia. The presentation will provide details on biomarkers of dementia, vascular risk factors and the association with apolipoprotein E in the Yoruba. The purpose will be to inspire early career researchers on possibilities and research strategies applicable in African populations