* | Carlsbergfondet
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Using single cell-RNA sequencing for understanding the diversity of the human and animals in-built GPS system

Forskningsinfrastruktur

What

Animals and insects have an in-built GPS (spatial navigation) system housed in the entorhinal cortex of the brain, which is only partially understood in mammals. A number of navigation-related functions have been discovered to lie in this brain region, such as, object recognition, processing speed movement and processing location, however the cells underlying these functions have been identified merely from their electrical firing characteristics and their gene profiles are unknown. There is a need to understand the complexity of the entorhinal cortex and how spatial navigation works. In this project we aim to study the spatial navigation system across several species at the single cell level in an effort to acquire an understanding of its unique and common properties across animals.

Why

This research will help to improve the classification of the cell types that are both common and unique to different species in the processing of navigation. Animals navigate using very different mechanism based on varying sensory inputs (e.g. auditory mechanisms in echolocation of bats compared to the detection of the earth's magnetic field in sea turtles). This project will help provide comprehensive insight into how different sensory information is processed which is relatively unknown outside of mammals. This project will also help to provide a more complete map of the cell types that exist in the entorhinal cortex as well as identify their roles in the mammalian spatial navigation system, which in many respects, is unknown.

How

We will first map the cell types and diversity of the spatial navigation system in bats, wolves, sea turtles, homing pigeons and leaf-cutter ants by performing RNA sequencing at the single cell level using the 10x Genomics system and analyze the data using bioinformatics. We will then further characterize the individual cells within the mammalian entorhinal cortex by combining single cell RNA sequencing with electrical measurements of neurons to match the cell's gene profile with its electrical profile using a large mammalian model, the pig. This will help to coordinate our molecular knowledge of the entorhinal cortex with the region's known functions.

SSR

The entorhinal cortex in humans is one of the first regions in the brain that succumbs to the detrimental effects of Alzheimer's disease. By understanding the basic makeup of the mammalian entorhinal cortex, scientists in the future will have the tools and know how to understand why the entorhinal cortex is affected first and why it is so vulnerable to this disease. One of the grand challenges for society is to find better treatments and potential cures for diseases that are prevalent in the aging population. This research project contributes to the basic biological understanding of the entorhinal cortex and may provide clues to foster future research in the Alzheimer's disease field.