Scientific jobs with a specific emphasis on biochemistry and molecular biology
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Prostate cancer is the most commonly occurring cancer in men and is the second leading cause of cancer mortality. A key pillar of current disease treatment relies on the inhibition of the cytochrome P450 17A (CYP17) enzyme, which causes a decline in cancer cell growth and invasiveness via the reduction of androgen steroid production (e.g. testosterone). An undesired consequence of active-site inhibition of this enzyme is the reduced production of other nonandrogenic steroids, such as cortisol which is critical for homeostasis and blood pressure control.
This project aims to circumvent the side effects associated with indiscriminate enzyme inhibition through the development of an inhibitor of CYP17 that blocks androgen production through its lyase activity whilst preserving the enzymes’ role in the biosynthesis of corticosteroids, such as cortisol through its hydroxylase activity. The project has just been awarded NHMRC funding and brings together a nationwide team of medicinal chemists, endocrinologists, computational and structural biologists, and a chemical biologist with expertise in structure, function, and
enzymology of CYP proteins. This team has significantly contributed to the understanding of how the CYP17 enzyme interacts with its accessory proteins: cytochrome P450 reductase which is critical for the supply of catalytic electrons, and cytochrome b5 (cyt b5) a known allosteric modulator of the dual activities of CYP17. The goal of the project is to selectively reduce androgen biosynthesis by inhibition of the allosteric changes caused by cyt b5 binding to CYP17A1, thereby inhibiting androgen synthesis but enabling cortisol synthesis.
As a PhD candidate working on this drug discovery project, you will be exposed to a wide variety of techniques including; protein expression, purification, characterisation and X-ray crystallography; in vitro enzymatic assays with quantification via LC-MS/MS; computational pharmacophore definition and ligand database screening; pharmacological analysis using surface plasmon resonance, biophysical characterization using differential scanning fluorimetry and dynamic light scattering. Specifically, working at the University of Adelaide under the supervision of Associate Professor Stephen Bell with co-supervision by Associate Professor Lisa Martin at Monash University, your project will be focussed on structural and chemical biology including:
- Recombinant protein production, purification and characterisation
- Analysis of steroid metabolites using GC-MS and LC-MS/MS
- Protein crystallisation and X-ray crystallography
- Molecular modelling
- Plasmid transfection of DNA into mammalian cell lines for protein production and co-expression for cell-based assays
The applicant will require the equivalent of a 1st class Honours or Masters by research degree.
Experience in working with proteins is desirable.
Expressions of Interest should be sent to firstname.lastname@example.org by Friday 16 April 2021.
PhD SCHOLARSHIP – HUDSON INSTITUTE OF MEDICAL RESEARCH AND UNIVERSITY OF MELBOURNE
A 3-year PhD scholarship is available in the Synnate Program, an NHMRC-funded collaboration between the Centre for Innate Immunity and Infectious Diseases at Hudson Institute, Monash University and the University of Melbourne. Scholarship is available at current APA rate.
Professor Paul Hertzog, Professor Christine Wells, Professor Elizabeth Hartland and Dr Sam Forster.
The reciprocal interactions between the mucosal epithelium, innate immune cells and the commensal microbial community play an important role in health and disease. However, most of these interactions are poorly understood and remain largely undefined. The NHMRC-funded Synnate program is seeking to recruit a suitably qualified and ambitious student to join a multidisciplinary research consortium to study how microbe-host interactions regulate mucosal immunity and elicit a healthy or disease state. This question will be addressed with integrated projects under the umbrella of the three themes in the areas of innate immune signalling, commensal and pathogen molecular microbiology, systems biology and tissue bio-engineering using technologies that may include iPSC-derived tissue systems, computational biology and microfluidics in organ-on-a-chip systems. Broad research questions include:
- What is the impact of the microbiome on the innate immune response?
- How is the microbiome influenced by the innate immune system and host genotype?
- How does disruption of the microbiome influence health and disease?
The goal of this work is the development of microbiome and/or immune-based diagnostics and therapeutics for human disease.
PhD RESEARCH AWARDS – CHILDREN’S MEDICAL RESEARCH INSTITUTE
Children’s Medical Research Institute (CMRI) is an award-winning state-of-the-art medical research facility, with over 100 full-time scientists dedicated
to researching the genes and proteins important for health and human development. CMRI is supported in part by its key fundraiser Jeans for Genes®. Our scientists are internationally recognised research leaders and foster excellence in postgraduate training. CMRI is located at Westmead, a major hub for research and medicine in NSW, and is affiliated with the University of Sydney.
Successful applicants will be awarded a Research Award, consisting of a generous top-up over the value of a university Research Training Program
(RTP) scholarship, for 4 years. Successful applicants will also be expected to apply for external scholarships with support from CMRI research leaders.
Projects are multidisciplinary with training in molecular and cellular biology techniques, with some involving mass spectrometry, proteomics,
bioinformatics, transgenic animals or live cell imaging.
Areas of CMRI research strength:
• Developmental biology and genetic disease
• Gene therapy
CMRI research units https://www.cmri.org.au/Research/Research-Units
PhD projects https://www.cmri.org.au/Research/For-Students
Contact supervisors directly for more details of projects.