Frazer Institute Winter Research projects
FI#1: Therapeutic modulation of hepatic stellate cells in liver cancer
Project title: FI#1 | Therapeutic modulation of hepatic stellate cells in liver cancer |
Project duration, hours of engagement | 4 weeks from 24th June to 19th July 2024 Hours expected per week: 25-30 hrs |
Location: | Woolloongabba: Translational Research Institute, Princess Alexandra Hospital |
Description: | Liver cancers, which include hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), are the fourth leading cause of cancer-related death worldwide. Transarterial chemoembolisation and systemic chemotherapy are the standard of care for patients with intermediate stage HCC and ICC. However, these chemotherapies only non-significantly improve the median survival, and patients still have very poor prognosis with a 5-year survival rate of 19% in Australia. Thus, strategies are urgently needed to improve chemotherapy efficacy in liver cancer. Over the past decades, increasing attention has been paid to the tumour microenvironment (TME). The TME not only plays a key role during liver cancer progression and metastasis but also has profound effects on therapeutic efficacy. As the major component of the TME within primary liver cancer, hepatic stellate cells (HSCs) undergo a phenotypic transformation due to environmental changes, known as “activation” or “transdifferentiation”. Activated HSCs primarily facilitate cancer initiation, progression and chemoresistance via secretion of growth factors and cytokines. Hence, activated HSCs emerge as a novel therapeutic target in liver cancer. Chemotherapy has been shown to serve as a “double-edged sword” through the modification of TME and HSC activation. However, the molecular mechanism underlying the HSC activation process induced by chemotherapy is poorly understood. Understanding the molecular mechanism of chemotherapy mediated HSC activation and evaluating potential HSC activation inhibitors or molecular targets will guide the development of effective therapy for liver cancer. |
Expected outcomes and deliverables: | The student can expect to learn cell culture and qPCR analysis and immunostaining of HSC activation markers. |
Suitable for: | This project is suitable for the student with a background in biomedical science, who is considering an Honours project in the field of liver cancer microenvironments and treatment. |
Primary Supervisor: | |
Contact info: | The supervisor MUST be contacted by students prior to submission of an application. |
FI#2: Characterising the synergism of inhibiting PI3K and AURKA using squamous cell carcinomas targeted therapies
Project title: FI#2 | Characterising the synergism of inhibiting PI3K and AURKA using squamous cell carcinomas targetted therapies |
Project duration, hours of engagement | 4 weeks from 24th June to 19th July 2024 Hours expected per week: 30 hrs |
Location: | Dutton Park Campus: Translational Research Institute |
Description: | Squamous cell carcinomas (SCCs), specifically cervical squamous cell carcinoma (CESC) and head and neck squamous cell carcinoma (HNSCC) are highly aggressive cancers. Surgery and chemoradiotherapy (CRT) continue to be the current treatment options against CESC and HNSCC in the clinic. Notably, the ability of SCCs to acquire resistance post-CRT continues to be the “Achilles heel” in the clinic. As such, patients experiencing aggressive relapse and metastatic disease have limited treatment options. Hence, novel therapeutic strategies and more targeted approaches are urgently needed to improve the clinical outcomes of these patients. Interstingly, these solid cancers are highly dependent on PI3K-AKT signaling pathway for tumor progression alongside showing high mitotic activity which is induced by overexpression of AURKA. We hypothesize that there exists an interdependency between these two pathways and hence dual inhibition of AURKA and PI3K/AKT pathway using small molecule inhibitors will induce cell death and regress tumour progression in vitro. |
Expected outcomes and deliverables: | The project comprises of performing in vitro techniques such as aseptic cell cuture; biochemical assays: cell proliefration, cell viability; molecular assays: RT-PCR, flow cytometry and immunoblotting. The students are expected to learn the basics. |
Suitable for: | Students with a keen interest in cell and molecular biology, biochemistry, and cell signaling will find this project very interesting. The project is ideal for Master's students, who are looking to complete an 8-unit research course after the winter semester. |
Primary Supervisor: | Frazer and Chandra Group |
Contact info: | The supervisor MUST be contacted by students prior to submission of an application. |
FI#3: Unravelling immune signalling networks
Project title: FI#3 | Unravelling immune signalling networks |
Project duration, hours of engagement | 4 weeks from 24th June to 19th July 2024 Hours expected per week: 20 to 36 hours |
Location: | Dutton Park Campus: Translational Research Institute |
Description: | The mucosal epithelium is a layer of cells that forms a protective shield around our organs including the lung, gut and skin. It defends these organs from harm caused by the environment. Immune cells located within this barrier are able to recognise damage from wounds, irritants or toxins and activate repair pathways. They are the first line of defense for the epithelial barrier—yet excessive activation of these pathways can cause unintended tissue damage. For example, in the gut, excessive damage can allow harmful bacteria to cross the gut wall and spread in the body, leading to serious infections. But our body has amazing repair systems. Most of the time, these repair mechanisms fix the damage appropriately, keeping our mucosal epithelium healthy – a remarkable feat given the myriad of physical and chemical stressors it experiences on a daily basis. This is because epithelia possess ‘smart’ sensing and signalling systems that allow them to detect problems and then repair the tissues. This project seeks to understand how immune cell communication and responses shape mucosal tissue protection. |
Expected outcomes and deliverables: | Through active engagement, participants can anticipate gaining a diverse range of skills, knowledge, and professional growth opportunities. |
Suitable for: | Students with a background in cellular biology, cancer, or immunology. |
Primary Supervisor: | |
Contact info: | The supervisor MUST be contacted by students prior to submission of an application. |