We improve human health by defining the underlying principles that control human biology and disease. Towards this goal, we develop and employ powerful new genomic technologies that show us how human disease develops, and how we can target the underlying causes. We have a focus on pain biology and other age-related diseases of the nervous system, and we apply new genomic technologies to identify genes and mechanisms controlling pain. We have a particular interest in better understanding how painful venoms hurt us, and how we can block these as well as use this knowledge to help treat chronic pain or other major diseases.
On the technical side, we primarily use pooled CRISPR screening to find new critical pain genes and pathways which we then investigate further using transgenic animals or human stem cells differentiated into human cells, tissues, and organoids. Therapeutically, we are targeting critical pain pathways using synthetic mRNA we design and evolve which we then encapsulate in lipid nanoparticles towards altering disease course for pain and other major diseases.
Professor Greg Neely completed his PhD in human lung immunology at the University of Calgary, Canada and went on to train in functional genomics with Josef Penninger at the Institute of Molecular Biotechnology in Vienna, Austria. Since 2011, he has been running his lab in Sydney using conserved functional genomics approaches to find novel human disease genes and pathways. Professor Neely's main interest is in how we feel pain and investigating at the molecular level how painful venoms hurt us. The team loves using functional screening systems like CRISPR or directed evolution to find new ways to control diseases like pain.
Our goal is to develop new ways to treat pain that target the underlying cause and not just to treat the symptoms. For this we need a better basic understanding of what is driving chronic pain including back pain, accidental injury, sciatica, cancer pain, diabetic neuropathy, shingles, or arthritis. To this end, we use new genome editing (CRISPR) and genetic techniques to find genes and pathways that are necessary and sufficient to drive pain diseases, and we study these new factors using fruit flies, mice, and human pain neurons grown from stem cells. From this we continue to develop new molecular-guided pain therapies, and are currently focused on mRNA-based therapeutics to treat pain, accelerating the chances of helping the >Billion people world-wide suffering with untreatable pain diseases
Venom mechanisms of action
We have developed functional pooled CRISPR screening systems to investigate how venoms induce painful signals, and we are using these screening systems to try and identify new pain pathways that we can then target therapeutically. We are also systematically evaluating venom toxins to attribute function and block uncharacterized venom toxins and peptides.
Directed evolution
We have recently developed PROTEUS, a mammalian directed evolution platform that allows us to evolve proteins towards new activities within the context of a mammalian cell. We are using this technology to develop new molecular biology tools for a variety or research or therapeutic applications. This approach is particularly useful to generate new synthetic mRNA that we can use to treat pain or other major diseases, and we also have an interest in mRNA-based antivirals.
We currently have several honours or PhD projects available in the lab.
The COVID-19 vaccine unlocked a new world of mRNA therapeutics. We have a number of projects available in the lab focused on developing new mRNA-based medicines for treating pain and other neurological diseases.
This project involves using and developing new CRISPR screening technologies to functionally characterise biological and chemical agents that cause pain.
We have developed new technologies to functionally screen human genes in the context of stem cell-derived organoids and from this have identified multiple new genes or pathways controlling brain development. This project involves using these new technologies to investigate what it means to be human.
This project involves using whole genome CRISPR screening to investigate how painful venoms hurt us. This information can then be used to develop novel antidotes, or exploited to generate novel therapeutics.
This project involves characterising human and mouse pain at the molecular level using single cell and special transcriptomics, and then targeting core disease pathways using new mRNA technologies.
We have recently developed a new directed evolution system (PROTEUS) that allows us to evolve proteins to have new activities in mammalian cells. This project involves evolving new genome editing tools for future research and therapeutic use.
Our previous efforts have primarily involved pooled CRISPR screening in vitro, followed by in vivo validation. With new technologies, we can now actually perform targeted screens in vivo, and this project
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