A5032411765- Microtubule and mitosis dynamics
- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Genetic and Kidney Cyst Diseases
- Assisted Reproductive Technology and Twin Pregnancy
- RNA Research and Splicing
- DNA Repair Mechanisms
- Reproductive Health and Technologies
- Pregnancy and preeclampsia studies
- Nuclear Structure and Function
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Neurogenesis and neuroplasticity mechanisms
- Endoplasmic Reticulum Stress and Disease
- Hereditary Neurological Disorders
- Birth, Development, and Health
- Animal Behavior and Reproduction
- Demographic Trends and Gender Preferences
- Genetics and Neurodevelopmental Disorders
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Skin and Cellular Biology Research
- Axon Guidance and Neuronal Signaling
- AI in cancer detection
The University of Melbourne
2021-2025
Biotechnology Institute
2024
Monash University
2017-2021
University of Otago
2014-2018
Discovery Institute
2017
The katanin microtubule-severing proteins are essential regulators of microtubule dynamics in a diverse range species. Here we have defined critical roles for the poorly characterised protein KATNAL2 multiple aspects spermatogenesis: initiation sperm tail growth from basal body, head shaping via manchette, acrosome attachment, and ultimately release. We present data suggesting that depending on context, can partner with regulatory KATNB1 or act autonomously. Moreover, our indicate may...
Abstract Analysis of testis histology is fundamental to the study male fertility, but it a slow task with high skill threshold. Here, we describe new neural network models for automated classification cell types and tubule stages from whole-slide brightfield images mouse testis. The type classifier recognizes 14 types, including multiple steps meiosis I prophase, an external validation accuracy 96%. stage distinguishes all 12 canonical 63%, which increases 96% when allowing ±1 tolerance. We...
Models of ageing predict that sperm function and fertility should decline with age as are exposed to free radical damage mutation accumulation. However, theory also suggests mating older males be beneficial for females because survival old is a demonstration male's high genetic and/or phenotypic quality. Consequently, declines in fitness may offset by indirect benefits exhibited offspring. While numerous studies have investigated age-based male fertility, none has taken the integrated...
Katanin microtubule-severing enzymes are crucial executers of microtubule regulation. Here, we have created an allelic loss-of-function series the katanin regulatory B-subunit KATNB1 in mice. We reveal that is master regulator all enzymatic A-subunits during mammalian spermatogenesis, wherein it required to maintain A-subunit abundance. Our data shows complete loss from germ cells incompatible with sperm production, and multiple new spermatogenesis functions for KATNB1, including essential...
Meiotic crossovers are required for accurate chromosome segregation and producing new allelic combinations. crossover numbers tightly regulated within a narrow range, despite an excess of initiating DNA double-strand breaks. Here, we reveal the tumor suppressor FANCM as meiotic anti-crossover factor in mammals. We use unique large-scale analyses with both single-gamete sequencing pedigree-based bulk-sequencing datasets to identify genome-wide increase frequencies Fancm-deficient mice....
The transition zone is a specialised gate at the base of cilia/flagella, which separates ciliary compartment from cytoplasm and strictly regulates protein entry. We identified potential new regulator male germ cell zone, CEP76. demonstrated that CEP76 was involved in selective entry incorporation key proteins required for sperm function fertility into ultimately tail. In mutant, tails were shorter immotile as consequence deficits essential motility including DNAH2 AKAP4, accumulated neck...
Abstract Dynein complexes are large, multi-unit assemblies involved in many biological processes via their critical roles protein transport and axoneme motility. Using next-generation sequencing of infertile men presenting with low or no sperm ejaculates, we identified damaging variants the dynein-related gene AXDND1 . We thus hypothesised that is a regulator male fertility. To test this hypothesis, produced knockout mouse model. Axdnd1 −/− males were sterile at all ages but presented an...
The development and function of male gametes is dependent on a dynamic microtubule network, yet how this regulated remains poorly understood. We have recently shown that severing, via the action meiotic AAA ATPase protein clade, plays crucial role in process. Here, we sought to elucidate roles spastin, an as-yet-unexplored member clade spermatogenesis. Using SpastKO/KO mouse model, reveal spastin loss resulted complete functional germ cells. Spastin assembly spindle. Consistent with failure,...
The purification of individual male germ cell populations is integral for the molecular and biochemical characterisation specific spermatogenic phases. Although a number more contemporary techniques have been developed, velocity sedimentation using STAPUT method remains as gold standard this purpose. gentle nature technique, wherein subpopulations are separated by at unit gravity, results in isolation viable high-purity cells. We provide an updated simplified step-by-step version protocol...
Abstract Microtubule severing regulates cytoskeletal rearrangement underlying various cellular functions. Katanin, a heterodimer, consisting of catalytic (p60) and regulatory (p80) subunits severs dynamic microtubules to modulate several stages cell division. The role p60 katanin in the mammalian brain with respect embryonic adult neurogenesis is poorly understood. Here, we generated Katna1 knockout mouse found that consistent critical mitosis, constitutive homozygous depletion lethal....
In 2022, the Society for Reproductive Biology came together in Christchurch New Zealand (NZ), its first face-to-face meeting since global COVID-19 pandemic. The showcased recent advancements reproductive research across a diverse range of themes relevant to human health and fertility, exotic species conservation, agricultural breeding practices. Here, we highlight key advances presented main meeting, including addressing opportunities challenges related First Nations people Australia NZ;...
Summary Katanin microtubule severing enzymes are potent M-phase regulators in oocytes and somatic cells. How the complex, evolutionarily critical, male mammalian meiotic spindle is sculpted remains unknown. Here, using multiple single double gene knockout mice, we reveal that canonical katanin A-subunit, KATNA1, its close paralogue, KATNAL1, together execute aspects of meiosis. We show KATNA1 KATNAL1 collectively regulate spindle, cytokinesis midbody abscission, addition to diverse spermatid...
Katanins, a class of microtubule-severing enzymes, are potent M-phase regulators in oocytes and somatic cells. How the complex evolutionarily crucial, male mammalian meiotic spindle is sculpted remains unknown. Here, using multiple single double gene knockout mice, we reveal that canonical katanin A-subunit KATNA1 its close paralogue KATNAL1 together execute aspects meiosis. We show collectively regulate spindle, cytokinesis midbody abscission, addition to diverse spermatid remodelling...
Abstract Dynein complexes are large, multi-unit assemblies involved in many biological processes including male fertility via their critical roles protein transport and axoneme motility. Previously we identified a pathogenic variant the dynein gene AXDND1 an infertile man. Subsequently additional four potentially compound heterozygous variants of unknown significance two men. We thus tested role mammalian by generating knockout mouse model. Axdnd1 -/- males were sterile at all ages but could...
Abstract Male infertility and meiotic arrest have been linked to M1AP , the gene encoding meiosis I associated protein. In mice, interacts with ZZS proteins SHOC1, TEX11, SPO16, which promote DNA class crossover formation during meiosis. To determine whether are involved in human male by disrupting formation, we screened for biallelic or hemizygous loss-of-function (LoF) variants genes select men a presumed protein deficiency; compiled N=10 N=4 SHOC1 N=9 first homozygous LoF variant SPO16 an...
Abstract The sperm mitochondrial sheath has proposed functions in structural support and energy production for motility. Here we define coiled coil domain containing protein 112, CCDC112, as crucial male fertility, specifically the assembly function of sheath. We unveiled a previously unrecognised process epididymal maturation. Sperm sheaths are structurally immature upon exiting testis continue to mature they transit from caput cauda epididymis. Data reveal critical role CCDC112...
Abstract The transition zone is a specialised gate at the base of cilia/flagella, which segregates ciliary compartment from cytoplasm and strictly regulates protein entry. In this study, we have identified CEP76 as an essential germ cell protein, involved in selective entry incorporation key proteins required for sperm function fertility into ultimately tail. its absence tails are shorter immotile consequence deficits motility including DNAH2 AKAP4, accumulate neck mutant. We demonstrate...
Abstract Alpha, beta and gamma tubulins are essential building blocks for all eukaryotic cells. The functions of the non-canonical tubulins, delta, epsilon zeta, however, remain poorly understood their requirement in mammalian development untested. Herein we have used a spermatogenesis model to define tubulin (TUBE1) function mice. We show that TUBE1 is multiple complex microtubule arrays, including meiotic spindle, axoneme manchette its absence, there dramatic loss germ cells male...
Abstract The development and function of male gametes is critically dependent on a dynamic microtubule network, yet how this regulated remains poorly understood. We have recently shown that severing, via the action meiotic AAA ATPase protein clade, plays critical role in process. Here, we sought to elucidate roles spastin, an as unexplored member clade spermatogenesis. Using Spast KO/KO mouse model, reveal spastin loss resulted complete functional germ cells. Spastin assembly spindle, its...