Mobile DNA in the mammalian primordial germline

This Earmarked Scholarship project is aligned with a recently awarded Category 1 research grant. It offers you the opportunity to work with leading researchers and contribute to large projects of national significance.

Supervisor – Dr Sandra

Approximately 2 weeks after a human embryo has implanted in the womb, germline specification occurs. In this process, a small population of primordial germ cells (PGCs) is set aside to form the germ lineage, ultimately giving rise to sperm and eggs. Thus, potentially before a woman is aware that she is pregnant, the embryo she is carrying contains the precursor cells destined to determine the genetic makeup of her grandchildren. This trans-generational link makes the genomic integrity of PGCs profoundly important.

Using mice as a model for mammalian development, our previous work has revealed that the genomes of early PGCs are mutagenised by the retrotransposon Long Interspersed Element 1 (LINE-1 or L1), a selfish genetic element or "jumping gene" that copies and pastes itself into new genomic locations. L1 activity in early PGCs leads to broad germline genetic mosaicism--the existence of genetically different cells within the same organism or tissue. L1 mutations arising in early PGCs are frequently transmitted to offspring, highlighting L1 mutagenesis as an ongoing source of new genetic diversity. However, the dynamics of L1 expression and retrotransposition in PGCs, how these activities are regulated, and the direct consequences of L1 dysregulation in PGCs remain incompletely understood.

The student leading this project will use in vitro assays to characterise L1 expression and retrotransposition during the cell fate transitions involved in PGC specification, identify cellular factors responsible for L1 regulation in this critical developmental niche, and take advantage of a well-characterised mouse model to elucidate the consequences of in vivo L1 dysregulation during PGC development.

Preferred educational background

Applications will be judged on a competitive basis taking into account the applicant's previous academic record, publication record, honours and awards, and employment history.

A working knowledge of genetics, genomics, molecular biology techniques; microscopy, flow cytometry, mouse handling and dissection, mouse embryonic stem cell culture, CRISPR-mediated genome editing, short-read (Illumina) and long-read (Oxford Nanopore; PacBio) genome and RNA sequencing would be of benefit to someone working on this project.

The applicant will demonstrate academic achievement in the field(s) of molecular genetics, genomics, developmental biology and the potential for scholastic success.

A background or knowledge of mobile DNA biology, developmental biology and germline development is highly desirable.

*The successful candidate must commence by Research Quarter 1, 2022. You should apply at least 3 months prior to the research quarter commencement date. International applicants may need to apply much earlier for visa reasons.

Apply now