Murdoch University

The exciting discovery of three new species of a small Australian marsupial has been tempered by the sad fact that each of the newly identified species of mulgara is likely already extinct. The exciting discovery of three new species of a small Australian marsupial has been tempered by the sad fact that each of the newly identified species of mulgara is likely already extinct. The Curtin University-led study has identified three new species of mulgaras, which are small carnivorous marsupials related to the Tasmanian Devil and quoll and that are important to the arid and semi-arid regions they inhabit in South Australia, Western Australia, the Northern Territory and Queensland. Led by Curtin PhD student Jake Newman-Martin, a collaboration with Dr Kenny Travouillon from the Western Australian Museum, Associate Professor Natalie Warburton from Murdoch University and Associate Professor Milo Barham and Dr Alison Blyth both from Curtin analysed preserved specimens of mulgaras from museums across the country, including bones found in caves which had previously not been identifiable. Mr Newman-Martin said the research had identified six species of mulgaras, as opposed to the previously accepted two and it also concluded that a third previously named mulgara was indeed a valid species. However, four of the proposed species appeared to be already extinct. "Known as 'ecosystem engineers', mulgaras are immensely important to the regions they inhabit as they help control the population of insects and small rodents and assist turning over the desert soils by burrowing," Mr Newman-Martin said. "By taking precise measurements of the skulls and teeth of preserved mulgara specimens, we were able to differentiate the species, the exact number of which had previously been the source of some debate. "Using the skulls and teeth of mulgaras had previously not been achievable because no study had documented and measured the bones in detail. Our study shows that mulgaras are actually far more diverse than previously thought." Research co-author Dr Kenny Travouillon, Curator of Mammalogy at the Western Australian Museum, said while the discovery of more species of mulgaras may sound like good news, the fact they were likely already extinct was disconcerting. "While Australia is renowned for its diverse and unique marsupials, it also has the highest mammalian extinction rate in the world, with many species suffering from the impacts of environmental degradation and introduced predators such as foxes and cats," Dr Travouillon said. "The most at-risk species are often overlooked small marsupials, which have suffered a great drop in their abundance and distribution since European colonisation. "The mulgaras may even represent the first recorded Australian extinction within the broader family of related animals (Dasyuridae) and are sadly disappearing with even less recognition than their now infamous 'cousins' the Tasmanian Tiger (Thylacine). "It is likely that many more undescribed species have already become extinct before they could be known to science, highlighting the need to better understand Australian wildlife and the growing threats to our ecosystems."

Increasing opportunities for up-close encounters with sharks and other animals are making wildlife tourism one of the fastest growing tourism sectors -- leading ecology experts to venture to one of the world's main sites to investigate the effects of tourism on endangered whale sharks. At Oslob in the Philippines, Flinders University's Southern Shark Ecology Group and Global Ecology Lab joined local Filipino researchers to measure how the daily feeding regimes for resident whale shark population might have affected their behaviour and physiology by assessing their activity and metabolic requirements. Increasing opportunities for up-close encounters with sharks and other animals are making wildlife tourism one of the fastest growing tourism sectors -- leading Australian ecology experts to venture to one of the world's main sites to investigate the effects of tourism on endangered whale sharks. At Oslob in the Philippines, Flinders University's Southern Shark Ecology Group and Global Ecology Lab joined local Filipino researchers to measure how the daily feeding regimes for resident whale shark population might have affected their behaviour and physiology by assessing their activity and metabolic requirements. Oslob is home to one of the world's largest whale shark (Rhincodon typus) tourism sites, and operators use 150kg to 400kg of food to attract the impressive animals to the picturesque location. In the 12 years since feeding whale sharks began, mass tourism at the location has increased the size of shark aggregation as well as changed shark behaviour, including 'desensitisation' to boat and human contact. "By fitting 16 whale sharks with small accelerometers, similar to a fitness tracker, we found their daily movements and resulting metabolic rate increased by up to 55% in response to their quest for food at the tourism site," says Flinders University Honours researcher Christine Barry, who is now doing a PhD at Murdoch University, Western Australia. "Our bioenergetics model suggests that providing about 220kg of food per day would be sufficient to offset higher metabolic rate driven by tourism. "However, the unknown long-term consequences of feeding whale sharks suggests that managers should focus on making changes to operating procedures to reduce the high activity we see at the site." Supported by the Harry Butler Institute at Murdoch University and the Australian Institute of Marine Science, Ms Barry hopes her current PhD project will support management at West Australia's Ningaloo Reef by measuring the importance of foraging ground for this vulnerable species. The Oslob study and data analysis were supported by Dr Adrian Gleiss from the Harry Butler Institute and Flinders University Professor Corey Bradshaw, who both contributed to the article just published in the journal Biological Conversation. Senior author Flinders University Professor Charlie Huveneers, Research Director of the Southern Shark Ecology Group, says the two-fold increase in whale shark activity was due to more rapid acceleration and altered tailbeat frequency and amplitude required by the sharks to move between and avoid each other and boats. "While wildlife tourism has many benefits, including educational and conservation opportunities, we need to be mindful of a range of possible negative effects on the movement and activity of the animals targeted by tourism. "Without adequate management and regulation, tourism could have a range of negative effects on whale sharks and their ecosystems, and therefore the industry relying on these whale sharks," he says. Ms Barry says whale shark tourism at Oslob is vital for international tourism and the local economy, and therefore understanding how to ensure sustainable practices is important. "Feeding whale sharks is becoming an increasingly common strategy for tourism in the Indo-Pacific region, so it is essential to continue investigating how this might be affecting the endangered whale shark," she says.

Autoimmune disease is active territory for drug research, and one reason why is that patients are poorly served by currently available therapies, contends Travis Murdoch, CEO of Human Immunology Biosciences. Many of these medicines bring a broad immunosuppressive approach that provides insufficient relief while introducing a range of side effects. Murdoch’s company is developing targeted alternatives. The startup identifies the cell type at the root of an autoimmune disorder, then develops drugs to either modulate those cells or eliminate them. Human Immunology Biosciences, or HI-Bio, hinted at its strategy earlier this year when it in-licensed a MorphoSys drug that is now its most advanced program. But the South San Franciso-based company aims to show that it’s more than a one-drug company. On Tuesday it revealed $120 million in financing to support a pipeline of medicines it claims can address the root causes of autoimmune diseases. HI-Bio was formed in early 2021, but Murdoch, a gastroenterologist, said he had been thinking about building this company since his time at the University of Calgary, where he focused on inflammatory bowel disease. The idea then was to develop drugs that take a precision approach to mediating disease that have known cellular drivers. ARCH Venture Partners and Monograph Capital shared that vision, and the venture capital firms incubated the startup. HI-Bio’s internal research focused on a type of immune cell called the mast cell. But the biotech also scouted for a drug candidate that could address “a potential high value target,” Murdoch said. The company found that candidate at MorphoSys. The in-licensed MorphoSys drug, felzartamab, addresses plasma cells, a type of white blood cell found in bone marrow that produces antibodies key to immune response. Dysfunction of these cells is associated with multiple immune-mediated diseases. Felzartamab is designed to target CD38, a protein abundant on mature plasma cells. CD38-targeting drugs are already available. Uncontrolled growth of plasma cells leads to a type of blood cancer called multiple myeloma. Johnson & Johnson’s Darzalex and Sanofi’s Sarclisa are both antibody drugs designed to target CD38 on multiple myeloma cells. HI-Bio believes this target also holds promise for treating the kidneys. “The link is a fascinating one,” Murdoch said. “Myeloma is a cancer of plasma cells. That marker is present on myeloma cells but it’s also present on normal plasma cells. There’s been much success in taking drugs that have been used for cancers of blood, lymphomas and the like, and applying them to autoimmune disease.” Plasma cells are antibody factories. In some autoimmune conditions, those factories produce too much of a particular antibody. The kidney diseases HI-Bio aims to treat are immunoglobulin A (IgA) nephropathy and membranous nephropathy. MorphoSys initially developed felzartamab under a partnership with Celgene (now part of Bristol Myers Squibb). The alliance ended in 2015 with MorphoSys regaining rights to the antibody. In 2017, I-Mab licensed rights to that drug in mainland China, Hong Kong, Macao, and Taiwan. I-Mab began developing the drug for multiple myeloma and it also has regulatory clearance in China to test it in lupus. Outside of China, MorphoSys had developed the drug for autoimmune diseases. MorphoSys’s Phase 1/2a research in multiple myeloma suggested how it could work. At the 2018 annual meeting of the American Society of Clinical Oncology, MorphoSys presented data showing preliminary efficacy against the trial’s multiple myeloma goals. The company also reported that felzartamab led to a reduction in M-protein, an abnormal protein fragment secreted by multiple myeloma cells known to have harmful effects on the kidney and immune system function. The immune system works by “memory” of sorts. When the immune system encounters an antigen it recognizes, it mounts a corresponding immune response. Antibodies produced by plasma cells are a source of this immune system memory. MorphoSys pointed to reduced tetanus antibody levels as a sign its drug had an effect on plasma cells. “We believe that the ability of felzartamab to deplete plasma cells was indirectly demonstrated by a reduction of Tetanus Toxoid vaccination titers no later than 2 weeks after the treatment start,” MorphoSys wrote in its 2021 annual report. In IgA nephropathy, HI-Bio needs to catch up to multiple contenders far along in development. Last December, Calliditas Therapeutics drug Tarpeyo became the first FDA approved therapy that reduces a protein associated with the kidney disorder. As a steroid, that drug offers a broad immunosuppressive effect. Vera Therapeutics’ aims to compete with mid-stage drug candidate atacicept, a fusion protein that’s designed to block two targets. Chinook Therapeutics has reached Phase 3 with atrasentan, a small molecule, and Phase 2 with BION-1301, an antibody. Novartis is vying to treat IgA nephropathy with iptacopan, a small molecule designed to block a complement system protein called factor B. HI-Bio licensed felzartamab and another antibody, now called HIB210, for $15 million up front and a 15% equity stake in the startup. MorphoSys could earn up to $1 billion in milestone payments, plus royalties from sales if one or both of the drugs reaches the market. Potential indications for HIB210, which targets a protein on neutrophils called C5aR1, have not yet been identified. That drug candidate is in Phase 1 testing. The potential indications for the biotech’s mast cell research are undisclosed, but these cells are associated with a range of allergic and inflammatory diseases. Third Harmonic Bio’s early clinical research with a mast cell-targeting small molecule licensed from Novartis fueled a $183 million IPO in September. Asked whether the $120 million in capital represents new money or cumulative financing, Murdoch declined to specify other than to say that Arch and Monograph are joined by Jeito Capital, unnamed institutional investors, and family offices. The cash will support the clinical development of the two lead programs as well as the ongoing discovery research in mast cells, he said. Public domain image by Flickr user Internet Archive Book Images