Multiple projects in molecular and cell biology related to cancer research

Project 1:  Role of Cep55 in ovarian cancer

Field: Cancers

Location: QIMR Berghofer (Herston)

TYpe of student:

• Higher Degree Research only i.e. PhD or MPhil (intercalated MD-PhD & MD-MPhil) 
• Honours students

Type of work:

• Wet lab work

Brief synopsis:

Cep55 is a cancer testis antigen, expressed during embryogenesis and silenced after birth in most tissues except testis. Notably, its expression is induced early during tumor formation, increased further with disease progression and is linked with worse prognosis in a wide-variety of cancers including ovarian cancer. Cep55 protein was identified and characterized in the lab of Professor Kum Kum Khanna. I am working with Professor Kum Kum Khanna at QIMR to study the growth and spread of a wide-variety of aggressive cancers including ovarian cancers using generation of knockout and overexpression mouse models and siRNA and shRNA-based depletion studies in cancer cell lines. However, siRNA-based targeting is not translatable in clinic and Cep55 does not have domain structure that is amenable to therapeutic targeting, as it mainly encompasses coil-coil motif which lacks highly defined binding pocket. Notably, we have used our knowledge of functional interactions of Cep55 and identified a peptide the blocks Cep55 interactions with its key partner proteins. In this project, we intend to verify extensively in preclinical studies that our novel peptide that inhibit functions of Cep55 can suppress growth and prevent the spread of human ovarian cancers in combination with conventional therapies following transplantation in mice.

Aim 1: To profile Cep55-targeting peptide for effects on proliferation, apoptosis, signalling,  migration and invasion of different ovarian cancer cell lines.

Aim 2: To demonstrate preclinically that anti-Cep55 targeting peptide stops ovarian cancer growth, spread and investigate synergy with clinically relevant therapies

Approaches

• Cell Culture and animal models 
• Immunoblotting and Immunodetection
• Flow Cytometry
• Immunofluorescence

Outcome: This project aims to test a new approach to target Cep55 in ovarian tumours. We propose to develop clinically relevant combinatorial approaches that if successful, could represent an entirely new Australian-invented treatment for patients with advanced ovarian cancer. This may be a direct and fast route to new-targeted therapies for such patients.

Contact person: Murugan Kalimutho. Email - murugan.kalimutho@qimrberghofer.edu.au

Project 2 : Projects in molecular and cell biology related to cancer research

Field:

• Cancers
• Pathology

Location: St Lucia

Type of student:  PhD and MPhil

Type of work: Wet lab work ​

My research team is focused on understanding the molecular switches (signalling pathways) that allow cells to respond to changes in their environment. We are particularly interested in the communication pathways that decide whether a cell grows and divides or arrests and dies.  Corrupting the pathways that make these life and death decision has major health consequences, and is the driving force behind many diseases including cancers, and neurodegenerative diseases, etc. By understanding how these decisions are made in molecular terms, in the long term, my team hopes to gain insights that can improve the treatment options for people affected by these diseases.

The overarching aim of my research is to is to systematically elucidate the biochemical mechanisms by which protein degradation enzymes (known as ubiquitin ligases) regulate cellular homeostasis. To date, the biological function of most ubiquitin ligases remains elusive as most have not been paired with substrates. Using interdisciplinary approaches incorporating proteomics, biochemistry, and molecular cell biology, my team seeks to delineate the components of signalling pathways implicated in the degradation of proteins implicated in cell division and cell death.  We focus particularly on understanding regulation of centrosomes, microtubules and, mitochondria, by the ubiquitin proteasome system. 

Contact person: Dr Julia Pagan. Email - j.pagan@uq.edu.au