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Universal DNA methylation age across mammalian tissues

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Type: Journal Article

Reference: Lu, A. T., et al. (2023). Universal DNA methylation age across mammalian tissues. Nature Aging. https://doi.org/10.1038/s43587-023-00462-6

Abstract

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

Tasmanian devil cathelicidins exhibit anticancer activity against Devil Facial Tumour Disease (DFTD) cells

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Type: Journal Article

Reference: Petrohilos, C., Patchett, A., Hogg, C.J. et al. Tasmanian devil cathelicidins exhibit anticancer activity against Devil Facial Tumour Disease (DFTD) cells. Science Report 13, 12698 (2023). doi: 10.1038/s41598-023-39901-0

Abstract

The Tasmanian devil (Sarcophilus harrisii) is endangered due to the spread of Devil Facial Tumour Disease (DFTD), a contagious cancer with no current treatment options. Here we test whether seven recently characterized Tasmanian devil cathelicidins are involved in cancer regulation. We measured DFTD cell viability in vitro following incubation with each of the seven peptides and describe the effect of each on gene expression in treated cells. Four cathelicidins (Saha-CATH3, 4, 5 and 6) were toxic to DFTD cells and caused general signs of cellular stress. The most toxic peptide (Saha-CATH5) also suppressed the ERBB and YAP1/TAZ signaling pathways, both of which have been identified as important drivers of cancer proliferation. Three cathelicidins induced inflammatory pathways in DFTD cells that may potentially recruit immune cells in vivo. This study suggests that devil cathelicidins have some anti-cancer and inflammatory functions and should be explored further to determine whether they have potential as treatment leads.

The genome sequence of the critically endangered Kroombit tinkerfrog

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Type: Journal Article

Reference: Farquharson, K., McLennan, E., Belov, K., & Hogg, C. (2023). The genome sequence of the critically endangered Kroombit tinkerfrog (Taudactylus pleione). F1000Research, 12(845). https://doi.org/10.12688/f1000research.138571.1

Abstract

The Kroombit tinkerfrog (Taudactylus pleione) is a stream-dwelling amphibian of the Myobatrachidae family. It is listed as Critically Endangered and is at high risk of extinction due to chytridiomycosis. Here, we provide the first genome assembly of the evolutionarily distinct Taudactylus genus. We sequenced PacBio HiFi reads to assemble a high-quality long-read genome and identified the mitochondrial genome. We also generated a global transcriptome from a tadpole to improve gene annotation. The genome was 5.52 Gb in length and consisted of 4,196 contigs with a contig N50 of 8.853 Mb and an L50 of 153. This study provides the first genomic resources for the Kroombit tinkerfrog to assist in future phylogenetic, environmental DNA, conservation breeding, and disease susceptibility studies.

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Koalas and Chlamydia: How can genomics help?

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by Luke Silver (PhD Student) 

The mention of a koala infected with Chlamydia will often be met with rounds of laughter or even concern, “can I get Chlamydia from touching a koala?” For koalas, Chlamydia is no laughing matter with up to 100% of individuals in some populations infected with the bacteria. In many cases infection will lead to blindness, “wet bottom” as a result of bladder infection, infertility and eventually death. Unfortunately, unlike humans, koalas are unable to go to the doctor and receive treatment for the infection. Often koalas are taken to veterinary hospitals after a human interaction (such as vehicle strike or a dog attack) and it is there the infection is noticed and treatment can be administered.

Genomics is the study of the genes and nucleotides contained within an individual’s genome. By studying the genomics of koalas, we have been able to identify important genes which play a vital role in helping a koala clear a Chlamydia infection. One of these genes is a part of the major histocompatibility complex, or MHC, known for its vital role in recognition of pathogens. We are now using the whole genomes of over 400 koalas to investigate how diverse the MHC genes of koalas are across their entire range from northern Queensland to South Australia. A high level of genetic diversity in the MHC results in an individual or population being able to recognise a wider array of pathogens and may be linked to the health of this endangered marsupial. Scientists in other labs are attempting to develop a vaccine which can prevent koalas from contracting the infection in the first place which has shown promising results in early phase testing.

Finally, fortunately you are unable to catch Chlamydia from holding or touching a koala as the species which infects koalas is different from the species which infects humans.

Author

Luke Silver

Luke Silver (PhD Student) is using genomic data to
investigate immune genes in Australian marsupials with a focus on koalas where he is using resequenced genomes to examine patterns of diversity in functional and neutral regions of the genome across the entire east coast of Australia. This work will be used to inform conservation and management decisions in the fight to save our threatened species.

lukesilver20

Adaptive Genetic Management of a Reintroduction Program from Captive Breeding to Metapopulation Management of an Arboreal Marsupial

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Type: Journal article

Reference: Pierson, J. C., Berry, L., Alexander, L., Anson, J., Birkett, M., Kemp, L., Pascoe, B. A., Farquharson, K. A., & Hogg, C. J. (2023). Adaptive Genetic Management of a Reintroduction Program from Captive Breeding to Metapopulation Management of an Arboreal Marsupial. Diversity, 15(7), 848. https://www.mdpi.com/1424-2818/15/7/848

Abstract

The application of genetic data to conservation management programs can be hindered by the mismatch in timelines for management decisions and the acquisition of genetic data, particularly genomic sequence data that may require outsourcing. While applying genetic principles where data are absent can provide general guidelines for actions, genetic data can often fine-tune actions through adaptive management. We describe the adaptive genetic management of the establishment of a metapopulation of a small arboreal marsupial, the red-tailed phascogale (Phascogale calura). Two captive breeding programs were established as source populations, with genetic principles applied to the establishment of the first program and empirical genetic data used to guide the establishment of the second program. Genetic data from both programs were then used to allocate founders to three new populations to create a metapopulation with diversity both within and among the sites. Building and maintaining the diversity of metapopulations when recovering threatened species will reduce pressure on the original source populations and increase the resilience of the species.

ABC Radio: The race to save Australia’s dirty frogs

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Simon Tang (2022 Honours Student) joined producer Shelby Traynor (ABC Radio) and Dr Jodi Rowley (Curator of Amphibian & Reptile Conservation Biology at the Australian Museum and UNSW) to talk about the pathogen-fighting peptides of frogs.

Listen to the full broadcast here: https://www.abc.net.au/radionational/programs/scienceshow/the-race-to-save-australia-s-dirty-frogs/102529160

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Making bioinformatics more accessible

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by Dr. Kate Farquharson (Post-doc)

In the AWGG lab, we are generating genomic resources for diverse Australian vertebrates, including birds, marsupials, amphibians and reptiles. However, following bioinformatics instructions can sometimes feel a bit like this:

Funny-on-sunday-how-to-draw-an-owl

And for non-model organisms, it can feel like being asked to draw an owl when you don’t even know what one looks like (or worse, imagine being given a picture of a human as a reference point). So, how do we make bioinformatics more accessible to people getting started? We have been working hard to carefully document our in-house workflows and contribute to public how-to guides, such as the Genome Assembly with Galaxy guide.

Documenting your work not only helps others but can be a useful way to remember what you have done before! Good documentation can help you to train others, present your methods and ensure your analysis is reproducible. Some tips for documenting your work include:

  • Always keep track of the software and versions used
  • Try out an editor such as Visual Studio Code, which allows you to easily insert code and scripts and integrates well with Github
  • Don’t forget your science brain! It can be very easy to follow a tutorial from start to finish but have no idea what the end result means. A few sentences to justify your approach and explain how you interpret your results will help others use your guide correctly

Good documentation is just one step we are working on as part of the Threatened Species Initiative and ARC Centre of Excellence in Peptides and Protein Science to make genomics and bioinformatics more accessible to conservation end-users.

Author

Dr Kate Farquharson

Dr Kate Farquharson is a Postdoctoral Research Associate in Bioinformatics within the ARC Centre of Excellence for Innovations in Peptide & Protein Science. She applies bioinformatic approaches to the assembly and annotation of genomes and transcriptomes of Australian species to identify targets for peptide discovery. Kate completed her PhD in the AWGG lab in 2020, where she used statistical and molecular genetic approaches to investigate adaptation to captivity in conservation breeding programs. Kate specialises in synthesising, analysing and interpreting data, and in communicating results clearly to a range of audiences.

@FarquharsonKate

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My Favorite Culture Shock: Australia’s Wildlife

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by Meadhbh Molloy (PhD Student)

I remember when I learned about the Tasmanian devil and DFTD in my Conservation Medicine textbook as a new master’s student in Virginia, USA. Since I was a child, I loved learning about different animals from all over the world but admittedly, I did know little about the Tasmanian devil. I was inspired by the many amazing researchers that were working on their conservation. I kept thinking about the Tasmanian devil throughout my master’s program and thought that maybe…I can go to Australia…and research Tasmanian devils as well for my PhD (I remember my first Zoom meeting with Carolyn…I was so excited!). After many more Zoom meetings, proposal drafts, a scholarship offer (thank you American Australian Association!), and a pandemic, I finally arrived in Sydney in August 2022. While I was eagerly looking forward to the first time I would see a Tasmanian devil, I have some honorable mentions of the other wildlife I have seen.

The mammals. This is my favorite taxonomic group, so I was most excited to see the mammals of Australia. I’ve seen potoroos scampering about, fruit bats flying at dusk, koalas at a sanctuary in Brisbane, an echidna crossing the road near Royal National Park, and of course the iconic kangaroo grazing right by my camping site in Jervis Bay. The Virginia opossum is our only native marsupial in North America. I was delighted to see brushtail possums (the arguably cuter cousin) in trees and sidewalks in the city, and digging through our food while camping. We also have a mammal that likes to dig through our stuff at campsites- the American black bear. It’s ok! You can put all your food up in a “bear bag” and it (mostly) helps.

The spiders. When I was researching my move to Australia, I came across a blog post titled “Every American remembers their first huntsman spider”. I thought “oh, well I’ll be in a city, they probably don’t get that big, assuming they are even there!”. Wrong. Listen, I appreciate spiders and their ecological role. I know they are probably “more scared of me than I am of them”. That does not mean I was calm and collected when I saw my first huntsman on the bathroom floor. Back at home we have big spiders (mainly wolf) that roam around, but they are no match for a huntsman’s speed! While I’m still a little scared of spiders, my definition of what a large spider is has certainly changed.

All the birds! It’s hard to pick a favorite Australian bird, but I would have to go with the kookaburra (even though one stole the sausage right out of my hands at a barbecue). The first time I heard one, it was 5:30am and I thought a monkey was outside my apartment window. We also don’t have wild parrots where I am from, so my phone is now filled with photos of beautiful white cockatoos and rainbow lorikeets. I remember going on a walk around my new neighborhood within the first few days of arriving. I saw a magnificent bird and told my roommate, Kimberley, about it when I returned. The bird had long legs, a beautifully contrasting white and black body, and was strutting around a park. Upon showing her a photo she said “oh yeah, a bin chicken”.  A bin chicken? Not the nicest name. I now understand why they are called that.

I’ve seen many other amazing animals while traveling around Australia, including saltwater crocodiles near Port Douglas, stunning marine life while snorkeling at the Great Barrier Reef, and even a camel when I visited Uluru (it was well-timed that I read “Tracks” by Robyn Davidson before my trip). I happened to feel particularly homesick when I went to Taronga Zoo on a nice spring day, only a couple months after I landed in Sydney. I arrived at the enclosure that I was most excited to see. I have waited a long time to come to Australia, and The Tasmanian devil has morphed from being the topic of one of my research chapters, to being a symbol of resilience and patience for my entire PhD. Immediately, the Tasmanian devil got up from a shady spot and walked across the enclosure to lie down in front of me. Did this little devil know it would be the first devil I would see in person, and knew the weight of this moment? Obviously not, it just wanted to sunbathe. Of all the animals I have seen so far, the Tasmanian devil remains to be my favorite. I look forward to seeing more of Australia’s wildlife before I return to the United States.

Author

Meadhbh Molloy (PhD Student) is characterising the gut microbiome profile of Tasmanian devils at multiple locations across Tasmania

@MeadhbhMolloy

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What my PhD has taught me: Turtles are awesome

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by Holly Nelson (PhD Student)

So, you probably think Tasmanian Devils are adorable and Koalas are super cute. Well, let me tell you about turtles and four quick reasons why they’re awesome.

1. Free rent: Imagine having a portable, self-contained home acquired at birth, the Sydney housing market would be the least of your worries. Unlike hermit crabs, the shells of these little keratin caravans are an extension of their spine and are the equivalent of a ribcage.

2. Solar panel: A turtle’s shell is more than its home. Not only is it a protective barrier against predators, turtles also use it to synthesise vitamin D from UV light which is needed for bone and shell growth. Not only this, turtles have nerve receptors in their shells, making them suckers for butt scratches.

3. Mixed signals: If you’ve ever seen a turtle slapping another turtle, one word, foreplay. Yes, turtles slap each other’s faces to convey affection and to attract a mate. A male turtle will slap a females face multiple times to make it clear he digs her. No mixed signals in the turtle world.

4. Realer than Jurassic World: Who needs CGI when you have real life dinosaurs still roaming the earth? These little guys date back over 220 million years to the time of the dinosaurs – woah! So don’t waste your time watching the new Jurassic world movie (wasn’t that good anyway), enjoy some turtle videos instead.

Although there’s a never-ending list of intriguing facts about turtles, hopefully one of these points has made you appreciate these underrated little critters a bit more.

Author

Holly Nelson (PhD Student) is working on how we can use genomics to revolutionise threatened species management. From genome assembly to downstream analyses using whole-genome data, Holly is using her work to answer genetic questions on the Bellinger River Snapping Turtle, Koala, and other threatened species. Her work, in partnership with the NSW Governments Saving Our Species program, aims to create more robust conservation strategies that can be developed and applied together with wildlife managers.

@hollyvnelson

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Diversity in the Dark: the hidden wonders of subterranean life

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by Toby Kovacs (PhD Student)

Australia is famous for its unique flora and fauna, harbouring some of the most unique and highly endemic groups of organisms. When I’m sitting around with my family discussing Australian biodiversity, often the first places we think of are the rainforests, the Great Barrier Reef or the hyper-biodiverse region of South Western Australia. We do unfortunately, often go without mentioning, the plethora of small, white and blind creepy crawlies living directly beneath our feet (quick have a look).

Not many people know that Australia contains an extraordinary level of subterranean (underground) life, living in the shadows. Scientists have long considered cave systems as natural ‘evolutionary laboratories’ due to the apparent simplicity of cave ecosystems. However, surprisingly few studies have contributed to our broad understanding of subterranean evolution. Subterranean fauna are characterised by their troglomorphic (cave adapted) features resulting from the loss of traits no longer required in the absence of light. These include the loss of pigment and eyes, as well as the elongation of antennae, legs and body. Although caves are the most well-known subterranean landscape, because of their accessibility and sick stalactites and stalagmites (Sydneysiders should check out the Jenolan Caves), they are not the only place you can find subterranean fauna (think a little deeper).

Modern subterranean surveys using deep bore holes and subterranean traps have found that inhabitable landscapes extend well beyond the observable caves. In the last decade a diverse array of life has been discovered in previously inaccessible non-cave subterranean landscapes. Australia, in particular the Western Australian Pilbara and Yilgarn regions, contains some of the most biodiverse non-cave subterranean landscapes known, predicted to contain ~3000 species (Halse 2014). Animals inhabit tiny, interconnected air pockets up to 150 m below the surface, where the air remains humid and relatively cool compared to the scorching surface temperatures. Here you can find spiders, cockroaches, beetles, isopods, centipedes, millipedes, pseudoscorpions, fish, crustaceans and even flies. Unfortunately, mining is abundant in these regions and conservation strategies for subterranean fauna are limited due to the vast majority of species being undescribed. However, genetic analysis provides a powerful tool for identifying species and assessing biodiversity in subterranean landscapes. If you’re interested in exploring the available specimen collections don’t hesitate to reach out, there’s so much work to be done!

 If you’re interested in visiting caves check out:

If you want to learn more about subterranean fauna check out:

  • Culver D.C., Pipan T. 2019. The Biology of Caves and Other Subterranean Habitats. Oxford University Press.
  • Halse S.A., Pearson G.B. 2014. Troglofauna in the vadose zone: Comparison of scraping and trapping results and sampling adequacy. Subterr. Biol. 13:17–34.

Author

Toby Kovacs

Toby Kovacs (PhD Student) I am using historical and modern Koala genomes to assess shifts in functional diversity over time, estimate genomic mutation rates, and test for signatures of local adaptation. I have a background in phylogenetics and molecular evolution and am completing my PhD in the Molecular Ecology, Evolution and Phylogenetics Lab in collaboration with the Australian Wildlife Genomics Group and the Center for Evolutionary Hologenomics (University of Copenhagen)

@tobykovacs