QIMR Berghofer Medical Research Institute Winter Research projects
QIMRB#1: Improving bone marrow/stem cell transplant outcomes through pre-transplant modulation of donor T cell function
Project title: QIMRB#1 | Improving bone marrow/stem cell transplant outcomes through pre-transplant modulation of donor T cell function |
Project duration, hours of engagement | 4 weeks from 24th June to 19th July 2024 Hours expected per week: 36 hours |
Location: | Herston: QIMR Berghofer |
Description: | Background & Hypothesis: Donor stem cell/bone marrow transplantation (allo-SCT/BMT) is an important curative therapy in the treatment of blood cancers, however its application is limited by serious complications such as graft-versus-host disease (GVHD) that have a significant impact on patient mortality and quality of life. Early inflammatory responses during preparative transplant conditioning initiate a cascade of adaptive immune responses that manifest as acute and/or chronic tissue damage in >50% of transplant recipients. GVHD treatment options are relatively limited and focused on immunosuppression and steroidal therapy, which are problematic due to opportunistic infection and refractory disease, therefore new therapies are urgently needed. Donor-derived T cells are known to be the key drivers of GVHD pathology but are also critical to maintain ongoing anti-tumour immunity, also known as Graft-versus-leukaemia (GVL) effects, which prevent cancer relapse in these patients. Identifying novel ways to target GVHD whilst maintaining GVL is key to improving patient outcomes. We propose that in vivo screening of potential therapeutic targets via manipulation of donor T cells pre-transplant will accelerate therapeutic development in this area. Aims & Approach: In this study, we will utilise recent advances in CRISPR-mediated gene therapy to modulate T cell function in naïve primary T cells for allo-SCT. This will involve optimisation, testing and validation of CRISPR gene editing of novel targets in naïve mouse T cells in vitro prior to transplant into allogeneic mice. |
Expected outcomes and deliverables: | Students will develop new skills in techniques relevant to immunology research such as immune cell isolation, gene modification and exposure to in vivo models of inflammatory disease. This is an ideal opportunity to gain experience in the laboratory. |
Suitable for: | We are looking for students with a strong interest in immunology who are keen to learn new techniques relevant to the field, e.g. flow cytometry, immune cell isolation, in vitro cell culture etc. |
Primary Supervisor: | A/Prof Kate Gartlan |
Contact info: | The supervisor MUST be contacted by students prior to submission of an application. |
QIMRB#2: Insect-specific viruses: novel agents to control the transmission of arboviral pathogens
Project title: QIMRB#2 | Insect-specific viruses: novel agents to control the transmission of arboviral pathogens |
Project duration, hours of engagement | 4 weeks from 24th June to 19th July 2024 Hours expected per week: 36 hours |
Location: | Herston: QIMR Berghofer |
Description: | Arthropod-borne viruses (arbovirus) transmitted by mosquitoes cause thousands of disease cases each year in Australia and remain a leading cause of morbidity and mortality internationally. For most arboviral diseases, there is no effective vaccine and mosquito control remains the only means of disease control. Mosquitoes are also hosts to numerous viruses that infect only insects (termed Insect Specific Viruses, or ISVs). ISVs are transmitted vertically from female insects to their offspring through infections of eggs. ISVs are benign to humans but can inhibit subsequent infection of mosquitoes by pathogenic viruses. While much work has been performed in cell culture, mosquito infections have not been evaluated for most ISVs. This project will determine the mosquito host range and vertical transmission efficiency of Insect-specific flaviviruses (ISFs) being evaluated as candidate biological control agents. Mosquitoes will be inoculated with ISFs during the pupal stage and the infection status of the resulting adult mosquitoes will be determined. Strains will be generated by selective breeding of infected mosquitoes and the infection status of their progeny will be tested. This will assist the selection of lines of mosquitoes with stable infections for further development as biological control agents against arboviruses. |
Expected outcomes and deliverables: | Students will gain experience in mosquito vector biology, working in unique and world class biosecurity facilities at QIMR Berghofer. Students will gain skills in virus assay (including performing tissue culture infectious dose assays), molecular biology. |
Suitable for: | Background knowledge in molecular biology, cell culture and/or virology would be beneficial but not essential. |
Primary Supervisor: | |
Contact info: | The supervisor MUST be contacted by students prior to submission of an application. |
QIMRB#3: Does the double edged (Eph –ephrin) sword effectively target GBM in the dish?
Project title: QIMRB#3 | Does the double edged (Eph –ephrin) sword effectively target GBM in the dish? |
Project duration, hours of engagement | 4 weeks from 24th June to 19th July 2024 Hours expected per week: 36 hours |
Location: | Herston: QIMR Berghofer |
Description: | Background: Glioblastoma (GBM) is an aggressive tumour with very poor prognosis and a median survival time of approximately 15 months. Novel therapies that can efficiently combat this disease are urgently required. We have generated compelling data showing discrete expression between EphA and its binding partner, an ephrinA. That have opposing roles in GBM and are expressed on the cell surface of the GBM tumour cell. We have generated well-characterised monoclonal antibodies (mAbs) against both these proteins and propose to use these simultaneously to effectively target this devastating disease. By targeting two proteins specifically expressed on the tumour and not normal brain, we aim to reduce toxicity while effectively killing most of the tumour. We have conjugated the mAbs with a drug to make antibody drug conjugates (ADCs) and need to test their killing efficacy in vitro. Aim: To validate EphA/ephrinA dual targeting using ADCs as an effective therapeutic strategy for GBM in vitro. Approaches used include: • In vitro killing assays to determine GBM cell killing and IC50 • Apoptosis/Cell death assays • Flow cytometry and Western blotting. |
Expected outcomes and deliverables: | Candidates will learn how to culture GBM cells, perform dose response curves and cell death assays to determine level of killing. |
Suitable for: | Candidates must have a liking for performing wet lab work. |
Primary Supervisor: | Professor Bryan Day Bryan.Day@qimrberghofer.edu.au Sid Faithfull Brain Cancer Laboratory Or Dr. Rochelle Dsouza |
Contact info: | The supervisor MUST be contacted by students prior to submission of an application. |
QIMRB#4: CAR T cell therapy for childhood cancer
Project title: QIMRB#4 | CAR T cell therapy for childhood cancer |
Project duration, hours of engagement | 4 weeks from 24th June to 19th July 2024 Hours expected per week: 28 - 36 hours |
Location: | Herston: QIMR Berghofer |
Description: | Chimeric Antigen Receptor (CAR) T cells are genetically modified immune cells that can recognise and kill cancer cells. They are a type of cancer immunotherapy that can be very effective against certain types of blood cancers and are now approved for use in patients. However, CAR T cells can only benefit a very small proportion of cancer patients at present. The aim of this project is to develop new types of CAR T cells directed at the disialoganglioside, GD2, which is expressed on the surface of certain cancers, including the childhood cancer, neuroblastoma. The project involves using molecular biology techniques to clone new types of CAR T cells, cell cultures to make retroviral vectors and CAR T cells, and using immunology assays to test the function of these new CAR T cells. It will provide exposure to the fields of cancer immunotherapy, genetic engineering and biotechnology, with a focus on clinical translation. |
Expected outcomes and deliverables: | Scholars will gain exposure to molecular cloning, gene modification with retroviral vectors, cell culture and immunological assays, such as flow cytometry. Scholars are expected to learn at least one or two techniques and be proficient in basic lab skills. |
Suitable for: | Students who are interested in cancer immunotherapy, biotechnology and clinical translation. Students who are interested in pursuing Honours or research higher degree are particularly encouraged to apply. |
Additional requirements: | This project requires evidence of vaccination for Hep B. Information will be provided with offer of placement. |
Primary Supervisor: | Translational Cancer Immunotherapy QIMR Berghofer Medical Research Institute |
Contact info: | The supervisor MUST be contacted by students prior to submission of an application. |