Evaluation of Network Biology Techniques for Discovering Biomarkers and understanding Mechanism of Action (MoA)

Location: Parkville, VIC

Duration: 4-6 months

Proposed start date: April 2019

Project Background

While in the past CSL and its competitors in the field of blood diseases (e.g. bleeding disorders, angioedema, humoral autoimmunity, etc.) have produced most of their treatments by fractionating donated human plasma, the landscape is changing with recombinant products progressively replacing plasma products, particularly in the developed world. This is driven by many factors, but perhaps most importantly the opportunity to design features into the molecules to improve treatment options. Consequently, many of the products currently in CSL’s pipeline are recombinants, and CSL is currently investing in large-scale recombinant manufacturing in anticipation of these products reaching the market in the near future. A targeted approach to the deployment of CSL products would facilitate the design of clinical trials and help understand mechanism of action (MoA), delivering therapeutic benefit to the optimal patient pool.

Complicating this goal is that patients with different upstream gene expression patterns may activate the same proteins downstream, leading to the same overall phenotype despite a different underlying cause. Thus different treatments would be needed for different patient groups. Network biology approaches may help to define neighbourhoods of genes and proteins involved in disease and may be used to identify novel biomarkers, evaluate the role of these modules in the MoA for CSL products and help to stratify patients for a better clinical trial design.

The main aim of this project is to explore the landscape of network biology and identify opportunities to improve CSL’s bioinformatic pipelines. We are therefore seeking a skilled PhD student in Bioinformatics / Computational Biology / Computer Science / Biomedical Sciences / Biochemistry and Molecular Biology with significant research experience in this field. The ideal candidate would have a PhD research topic that directly relates to understanding gene regulatory networks from gene expression data, plus a strong focus on the biological interpretation of findings. Third year students would be preferred.

Research to be Conducted

Key objectives that the company hopes to achieve through the internship:

  1. Identify and evaluate existing tools for constructing de novo biological networks from publicly available databases and experimental data. Select the most appropriate tool or design one.
  2. Perform co-expression network analysis using gene expression data. Combine pathway analysis with GWAS data from in-house and publicly available datasets to infer gene regulatory networks.
  3. Using pathway information, identify possible biomarkers or mechanisms of action for specific diseases.
  4. Develop recommendations for integrating multi-omics analyses into existing pharmacological research workflows.

Some pre-identified software resources:

  • Cytoscape
  • GeneMANIA
  • NDEx
  • WikiPathways
  • CyPath2 App

Resources available at CSL to assist this research project:

  • In-house experts
  • In-house high-performance computing platform
  • A desk space and standard CSL laptop + monitor.

Skills Required

We are looking for a PhD student with the following:

ESSENTIAL

  • Currently doing a PhD in bioinformatics, computational biology, computer science, biomedical sciences, biochemistry or molecular biology
  • Familiarity with biological network analysis, biological signal transduction, and/or bioinformatics methodologies
  • Strong English communication skills (verbal and written)
  • Strong programming experience, preferably in Python or R

DESIRABLE

  • Experience using Cytoscape and molecular interaction databases

Expected Outcomes

The intern will assist CSL scientists in evaluating network biology techniques and their application to biomarker discovery and deciphering MoAs. The intern may prototype a new computational tool, if appropriate, or use one or more existing tools. The computational tools developed during this project will be used to extend CSL’s in-house RNASeq analysis workflow. The initial project will focus on airway disease as a main indication, but future applications may involve re-purposing this framework to analyse other biological networks.

The primary purpose of the internship is for the education of the intern by enabling them to apply their expertise to a real-world problem, experience the company environment, develop workplace skills and improve their work-readiness. It is expected that the intern will work closely with industry staff who will mentor them throughout the internship. The project will develop the intern’s understanding of the ethical drug development process and the criticality of a multidisciplinary approach to progress a pre-clinical drug candidate through the clinic for the treatment of diseases with significant unmet medical need.

Additional Details

The intern will receive $3,000 per month of the internship, usually in the form of stipend payments.

It is expected that the intern will primarily undertake this research project during regular business hours, spending at least 80% of their time on-site with the industry partner.  The intern will be expected to maintain contact with their academic mentor throughout the internship either through face-to-face or phone meetings as appropriate.

The intern and their academic mentor will have the opportunity to negotiate the project’s scope, milestones and timeline during the project planning stage.

Applications Close

6 March 2019

Reference

APR – 0841