Projects

Our available projects revolve around the major lab themes:

  1. The core processes of sperm construction and function
  2. Understanding the genetic causes of male infertility

CURRENT PROJECTS – get in contact now for 2022 Honours, Masters and PhD:

 

  1. Title: Investigating the role of MROH9 in spermatogenesis and male fertility.
    Location:
    Bio21 Institute
    Supervisors: Dr. Brendan Houston, Prof. Moira O’Bryan
    Contact: moira.obryan@unimelb.edu.au
    Project type: Hons or MSc project

Background and Project Description

Male infertility is a common condition that affects at least 7% of men and is often caused by genetic factors. In line with the variety of cellular processes involved in sperm production, the testis expresses around 17,000 genes and the role of many of these is unknown. As part of a collaborative role in the International Male Infertility Genomics Consortium, we have identified genetic variants in Maestro Heat Like Repeat Family Member 9 (MROH9) to be a likely cause of infertility in several men who do not produce sperm. MROH9, also known as ARMC11, is an unexplored gene/protein and nothing has been published regarding its function. Other proteins in the ARMC family are, however, known to play essential roles in the production of functional sperm. We have thus generated a knockout mouse model to define the role of MROH9/ARMC11 in male fertility.

This project will involve fertility ‘phenotyping’ of knockout males using a standard pipeline and expert training available in the Male Infertility and Germ Cell Biology lab. You will assess whether knockout males are infertile and validate the knockout model. The student will also define the consequences of MROH9 loss on the histology of the testis and male germ cells, daily sperm production and sperm function, if they are present. You will also define the localization of MROH9 in the normal testis.

 

  1. Title: Inter-species differences in sperm structure.
    Location:
    Bio21 Institute
    Supervisors: Dr. Brendan Houston, Dr Jessica Dunleavy, Prof. Moira O’Bryan
    Contact: moira.obryan@unimelb.edu.au
    Project type: Hons or MSc project

Background and Project Description

Sperm structure varies greatly between species. The reason for, and the consequences of, these differences are poorly understood. Such differences occur in the sperm head, and the tail including in the mitochondrial sheath. In sperm, mitochondria are contained with the midpiece and separated from the remainder of the cell where they generate energy for sperm function, including for sperm tail motility.

This project will involve an investigation of the sperm structure at a three-dimensional level. This will include an analysis of sperm head shape, the mitochondrial sheath structure and the sperm tail as a whole and comparisons across species (mammals, fish, insects, etc.) using scanning and transmission electron microscopy. Collectively, this will allow insights into species differences in sperm structure and function and may feed into our understanding of the consequences of differences in evolutionary pressures.

 

  1. Title: The role of male-derived cysteine-rich secretory proteins (CRISPs) in modulating the immune response in the female reproductive tract.
    Location:
    Bio21 Institute
    Supervisors: Dr. Brendan Houston, Prof. Moira O’Bryan
    Contact: moira.obryan@unimelb.edu.au
    Project type: Hons or MSc project

Background and Project Description

CRISPs are a family of proteins that are highly enriched in the male reproductive tract, including in seminal plasma. We have recently generated a novel knockout mouse model wherein CRISPs have been removed from seminal plasma. These mice are infertile. Within this project, you will help to validate the gene deletion in this mouse model. You will also investigate the consequences of CRISP loss on both male germ cell function and the dynamics of the immune response within the female tract. This project will involve a histological analysis of male and female reproductive tissues, immunochemistry and potentially recombinant protein production and replacement studies. This project has broad relevance to male infertility, including in the agricultural sector where differences in semen CRISPs have been associated with sub-fertility in horses and camels.

 

  1. Title: The role of dynein transport in sperm tail formation: a novel dynein gene identified in an infertile man
    Location:
    Bio21 Institute
    Supervisors: Dr. Brendan Houston, Dr. Jess Dunleavy, Prof. Moira O’Bryan
    Contact: brendan.houston@unimelb.edu.au
    Project type: MSc or PhD project

Background and Project Description

Sperm tail formation is a complex event that occurs in spermatids in the last half of spermatogenesis. After the core axoneme structure of the tail is seeded, it is supplemented with accessory structures and essential motility proteins. Sperm tail development requires highly regulated protein transport that leverages on overlapping cytoskeletal elements in the elongating spermatid. Motor proteins, including kinesins and dyneins that travel along microtubules, and myosins that travel along actin filaments, play a major role in the transport of essential proteins and cargoes required for this process. However, the overall mechanisms of protein transport in male germ cells are still unclear, including the role of male germ cell-specific motor protein subunits. We have recently identified the gene Axdnd1 (axonemal dynein light chain containing 1) to be essential for sperm tail formation and male fertility in men and mice. AXDND1 is a male germ cell enriched, novel dynein subunit that we hypothesise plays an essential role in trafficking cargoes for sperm tail development and other aspects of spermatid differentiation. Sperm generated by Axdnd1 knockout mice are highly abnormal, displaying coiled tails and no capacity for sperm motility.

This project will investigate the role of AXDND1 in protein transport through a determination of its interacting protein partners. You will utilise a targeted (predicted interacting proteins) and explorative screen to explore AXDND1 protein interactions in the testis. This will also involve validation of protein interactions in male germ cells and cell lines, and protein/mRNA localisation studies.

 

Other areas of interest:

Understanding the role of microtubule severing enzymes in spermatogenesis, using multiple conditional knockout mouse models
Email moira.obryan@unimelb.edu.au or jessica.dunleavy@unimelb.edu.au for more info

Defining the role of a novel centriole protein in spermiogenesis and its role in sperm motility
Email brendan.houston@unimelb.edu.au for more info

Characterising novel conditional spermiogenesis drivers in Drosophila melanogaster
Email brendan.houston@unimelb.edu.au for more info