Male infertility and germ cell biology
We aim to identify key mechanisms required for male germ cell development, the aetiology of human male infertility and the interplay between fertility and health. This is achieved using a range of genomic, biochemical and cell biological methods, including the development of unique model systems.
Male fertility research provides data of three-fold value:
- Male infertility is a major medical problem affecting 1 in 20 Australian men of reproductive age. For the majority of these men the underlying aetiology is unknown and thus, targeted therapies cannot be applied
- An enhanced understanding of the mechanisms of spermatogenesis (the process of sperm production) may provide opportunities for contraceptive intervention;
- Spermatogenesis has proven to be an extremely productive system within which to discover molecules and processes of fundamental importance to cell biology and human health.
Each of the fields of stem cells, cilia biology, epigenetics and DNA repair had their origins in the testis. In order to produce 1,000 sperm per heart beat, as humans do, stem cells must divide continuously, the DNA breaks inherent in cell division and in meiosis in particular must be faithfully and rapidly repaired, and the thousands of genes involved in forming the highly condensed, and motile sperm must be tightly regulated at each of a transcriptional, translational and post-translational level. Unlike the majority of tissues wherein these processes occur only in discrete developmental processes or in response to challenge, within the testis they occur continuously and on a large scale, thus making spermatogenesis an outstanding system within which to discover novel pathways and to define their in vivo function.
Cilia/flagellar development and function, genetic causes of human infertility, the importance of epigenetic regulation in male fertility, sperm head shaping and the transcriptional and translational control of germ cell-expressed genes.
We are often looking to take on students in the lab. Our available projects revolve around the major lab themes:
- The core processes of sperm construction and function
- Understanding the genetic causes of male infertility
Investigating the processes of sperm mitochondrial coiling and fusion, using a novel knockout mouse model wherein these processes are dysfunctional
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Understanding the role of microtubule severing enzymes in spermatogenesis, using multiple conditional knockout mouse models
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Defining the role of a novel centriole protein in spermiogenesis and its role in sperm motility
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Characterising novel conditional spermiogenesis drivers in Drosophila melanogaster
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Prof. Moira O’Bryan
Lab head and Dean of Science at The University of Melbourne
Moira is a world leader in the fields of male fertility, male germ cell development and sperm function. She is an ARC college of experts panel member (2018-2020), has delivered numerous plenary presentations, has won multiple high-ranking awards, and has held continuous grants from the ARC and NHMRC for 26 years. Her lab has two largely overlapping themes:
- Understanding the mechanisms of sperm production and function, i.e. ‘how to build functional sperm’
- Defining the genetic causes of male infertility
Moira is a steering member of the International Male Infertility Genomics Consortium
Dr. Brendan Houston
Postdoctoral Research Fellow
Brendan works on defining novel genetic causes of human male infertility using a variety of model systems (mice, flies and cultured cells). These models are based on high confidence genetic variants found in infertile men from the International Male Infertility Genomics Consortium and The Genetics of Male Infertility Initiative. He was awarded his PhD from The University of Newcastle, Australia (supervised by L/Prof. John Aitken, Prof. Brett Nixon, Dr. Geoffry De Iuliis and Dr. Bruce King) in 2018 and has worked in the O’Bryan lab since. Brendan is a past Rutherford fellow (UUKi) and is available as a PhD supervisor, so feel free to contact him for more info.
Dr. Jessica Dunleavy
Postdoctoral Research Fellow
Jess works on understanding the fundamental mechanisms that drive mammalian sperm production using multiple knockout mouse models. Her research mainly centres around cytoskeletal dynamics and their relevance to male fertility, with particular focus on the unique cytoskeletal structures, regulators and protein transport pathways that feature during male meiosis and spermatid remodeling. She was awarded her PhD from Monash University (supervised by Prof. Moira O’Bryan and Prof. John Carroll) in 2018. Prior to that, she worked under the supervision of Prof. Neil Gemmell and Dr Sheri Johnson at the University of Otago, studying the effect of paternal age on fertility in Zebrafish. Jess and Moira currently hold an NHMRC Ideas Grant investigating the mechanisms of mitochondrial loading onto the sperm tail during spermiogenesis. Jess is available as a PhD supervisor, so feel free to contact her for more info.
Anne O’Connor (Bsc(Hons))
Anne manages the lab and has significant experience in working with protein production and assessment, hormone assays, antibody development and various other techniques. Anne has worked with Moira for many years and has been involved in the characterisation of multiple knockout mouse models, including several mutagenesis studies.
Jo Merriner (Bsc(Hons))
Jo is a research assistant with significant experience in histology and electron microscopy, sperm functional assessment and confocal/EM imaging. Jo has worked with Moira for many years and has been involved in the characterisation of multiple knockout mouse models, including several mutagenesis studies.
Dr. Denis Korneev
Postdoctoral Research Fellow
Denis is a biophysicist who works on the development of electron microscopy techniques (advanced SEM and FIB-SEM) and image processing. He has recently developed a technique to study the outer sperm tail accessory structures and is working on a method to perform large-volume 3D imaging of spermatogenesis at an EM level. He works at Monash University with Professor Alex de Marco and at The University of Melbourne with Moira and the lab
Sam investigates the genetic causes of male infertility using flies and mice. Moira is his main supervisor and he is co-supervised by Prof. Joris Veltman (Newcastle University), Dr. Jess Dunleavy (Melbourne) and Dr. Travis Johnson (Monash)
Amy investigates the genetic causes of male infertility using flies and mice. Moira is her main supervisor and she is co-supervised by Prof. Don Conrad (Oregon Primate Centre), Dr. Brendan Houston (Melbourne) and Dr. Richard Burke (Monash).
Gemma investigates the role of tubulins in spermatogenesis using mice and cell culture methods. Moira is her main supervisor and she is co-supervised by Dr. Jessica Dunleavy (Melbourne) and Dr. Jennifer Zenker (Monash).
Lachlan investigates the genetic causes of male infertility using flies and mice. He is situated at Monash University and is co-supervised by Prof. Moira O’Bryan, Dr. Richard Burke (Monash) and Dr. Daniela Fietz (Giessen).
Kate is an embryologist with Monash IVF who is working to generate novel techniques to intricately measure sperm motility as a readout of sperm quality. She is co-supervised by Prof. Moira O’Bryan and Dr. Reza Nosrati.
Lauren does all our genotyping and is currently studying a Bachelor of Science at Monash University.
Honours students in 2021
Maddison investigates the role of the microtubule severing enzyme KATNAL1 in spermatogenesis using mouse knockout models. She is supervised by Dr. Jessica Dunleavy.
Hidenobu Okuda (2015-2018), now working in Japan as a urologist
Avinash Gaikad (2020-2021), now working with Prof. Dr. Frank Tüttelmann in Münster, Germany
Christiane Pleuger (2017-2019), now working with Prof. Andreas Meinhardt in Giessen, Germany
Jinghua Hu – submitted (2017-2019), now working in Canada as a postdoc
Gemma Stathatos 2019
Sam Cheers 2018
Daniel Moya Aguirre 2018
Maddy Cooper 2017
Kathryn Wozniak 2017
Giorgina Maxwell 2020
See all of Moira’s publications:
The Sertoli cell expressed gene secernin-1 (Scrn1) is dispensable for male fertility in the mouse – Developmental Dynamics
Bacteriophages targeting Acinetobacter baumannii capsule induce antimicrobial resensitization – Nature Microbiology
Deleterious variants in X-linked CFAP47 induce asthenoteratozoospermia and primary male infertility – The American Journal of Human Genetics
Disruption of human meiotic telomere complex genes TERB1, TERB2 and MAJIN in men with non-obstructive azoospermia – Human Genetics
Programmed Cell Death 2-like (Pdcd2l) Is Required for Mouse Embryonic Development – G3: Genes, Genomes, Genetics
Deficiency of the Tbc1d21 gene causes male infertility with morphological abnormalities of the sperm mitochondria and flagellum in mice – PLoS Genetics
Bi-allelic mutations in M1AP are a frequent cause of meiotic arrest and severely impaired spermatogenesis leading to male infertility – The American Journal of Human Genetics
CRISP3 expression drives prostate cancer invasion and progression – Endocrine-related Cancer
The functions of CAP superfamily proteins in mammalian fertility and disease – Human Reproduction Update
Reproduction in a polluted world: implications for wildlife – Reproduction
Haprin‐deficient spermatozoa are incapable of in vitro fertilization – Molecular Reproduction and Development
Haploid male germ cells—the Grand Central Station of protein transport – Human Reproduction Update
A framework for high-resolution phenotyping of candidate male infertility mutants: from human to mouse – Human Genetics
Expression and purification of recombinant mouse CRISP4 using a baculovirus system – Protein Expression and Purification
Exome sequencing reveals novel causes as well as new candidate genes for human globozoospermia – Human Reproduction
Health and fertility of ICSI-conceived young men: study protocol – Human Reproduction Open
GLIPR1L1 is an IZUMO-binding protein required for optimal fertilization in the mouse – BMC Biology
CBE1 is a manchette-and mitochondria-associated protein with a potential role in somatic cell proliferation – Endocrinology
An optimised STAPUT method for the purification of mouse spermatocyte and spermatid populations – Molecular Human Reproduction
Rare mutations in the complement regulatory gene CSMD1 are associated with male and female infertility – Nature Communications
Germ cell arrest associated with a SETX mutation in ataxia oculomotor apraxia type 2 – Reproductive Biomedicine Online
Context-specific behavioural changes induced by exposure to an androgenic endocrine disruptor – Science of the Total Environment
CRISP2 is a regulator of multiple aspects of sperm function and male fertility – Endocrinology
Impact of the widespread pharmaceutical pollutant fluoxetine on behaviour and sperm traits in a freshwater fish – Science of the Total Environment
The cytoskeleton in spermatogenesis – Reproduction
Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance – BMC Biology
Long‐term follow‐up of ICSI‐conceived offspring compared with spontaneously conceived offspring: a systematic review of health outcomes beyond the neonatal period – Andrology
Cep55 overexpression causes male‐specific sterility in mice by suppressing Foxo1 nuclear retention through sustained activation of PI3K/Akt signaling – The FASEB Journal
Bi-allelic recessive loss-of-function variants in FANCM cause non-obstructive azoospermia – The American Journal of Human Genetics
GSK3 inhibition, but not epigenetic remodeling, mediates efficient derivation of germline embryonic stem cells from nonobese diabetic mice – Stem Cell Research
The antidepressant fluoxetine alters mechanisms of pre-and post-copulatory sexual selection in the eastern mosquitofish (Gambusia holbrooki) – Environmental Pollution
Epididymal cysteine-rich secretory proteins are required for epididymal sperm maturation and optimal sperm function – Molecular Human Reproduction
Prof. Moira O’Bryan – Dean of Science
Old Geology Building (Building 155)
The University of Melbourne
Executive Assistant – Liliana Mendes