Faculty/School

Faculty of Health

School of Biomedical Sciences

Topic status

In progress.

Research centre

Centre for Genomics and Personalised Health

Supervisors

Professor Jyotsna Batra
Position
Professor
Division / Faculty
Faculty of Health
Dr Sri Srinivasan
Position
Postdoctoral Fellow
Division / Faculty
Faculty of Health

Overview

Prostate cancer (PCa) is the most heritable of all major cancers, with 57% driven by genetic factors. Genome-wide association studies (GWAS) have identified a PCa-risk associated non-synonymous rs17632542 (Ile163Thr substitution) single nucleotide polymorphism (SNP), in the crucial kallikrein-3 (KLK3) gene. Prostate-specific antigen (encoded by KLK3) is the standard biomarker for PCa. Our fine-mapping studies through the PRACTICAL PCa consortium in 82,591 PCa cases and 61,213 matched controls, reported, this coding rs17632542 SNP significantly predisposes patients to present with aggressive PCa and poor survival. However, the molecular mechanisms underlying this risk association is not yet explored.

Aims:

1. Perform rs17632542 SNP knock-in using CRISPR editing in cell lines

2. Evaluate the cellular effect of the rs17632542 SNP using CRISPR-edited cell line models.

This multi-disciplinary project proposes to combine expertise in genetic engineering and in vitro cell line models involving CRISPR and expertise in cellular assays to elucidate the role of PSA and the SNP-encoded PSA isoform in prostate cancer etiology and disease progression.

References:

  1. Srinivasan S, Kryza T, Batra J, Clements J. Remodelling of the tumour microenvironment by the kallikrein-related peptidases. Vol. 22, Nature Reviews Cancer. Nature Research; 2022. p. 223–38.
  2. Batra J, Srinivasan S, Kryza T, Bock N, Tse BW, Sokolowski KA, et al. Biochemical activity induced by a germline variation in KLK3 (PSA) associates with cellular function and clinical outcome in prostate cancer. 2023; Available from: https://doi.org/10.21203/rs.3.rs-2650312/v1.
  3. Moradi A, Srinivasan S, Clements J, Batra J. Beyond the biomarker role: prostate-specific antigen (PSA) in the prostate cancer microenvironment. Vol. 38, Cancer and Metastasis Reviews. Springer; 2019. p. 333–46.
  4. Srinivasan S.,...Batra J. (2019) Prostate Cancer Risk-Associated Single-Nucleotide Polymorphism Affects Prostate-Specific Antigen Glycosylation and Its Function. Clin Chem, 65, e1-e9.
  5. Kote-Jarai Z., ...Batra J et al. (2011) Identification of a novel prostate cancer susceptibility variant in the KLK3 gene transcript. Hum Genet, 129, 687-694.

Research engagement

  • Cell culture
  • CRISPR
  • Proliferation, migration and invasion assays

Research activities

The student will work closely and receive training from Dr Sri Srinivasan along with mentorship and guidance from Prof Jyotsna Batra.

Outcomes

This study will lead to identification of the function of rs17632542 SNP explaining the link to PCa pathogenesis and clarification on the impact of the SNP on PSA protein expression and splicing.

Skills and experience

No specific skills are required, other than enthusiasm and keen interest in learning and understanding cancer biology.

Start date

1 November, 2024

End date

21 February, 2025

Location

Translational Research Institute

Keywords

Contact

Srilakshmi Srinivasan, s1.srinivasan@qut.edu.au