Tim Hughes' project group: Functional Molecular Mechanisms in Bipolar Disorder

Publication list available from Google Scholar 

Main focus: understanding the molecular mechanisms of neuro-psychiatric disorders
The internal molecular working of the human brain determines an individual's behaviour and its malfunction has severe consequences on affected individuals and their families. However, because of this unique and essential role, access to and experimentation on the brain is very restricted. As a result, the scientific community has limited understanding of both the etiology of polygenic neuro-psychiatric disorders and of the pathways through which current treatments act.

In the past decade, progress has been achieved at the DNA level through genome-wide association studies (GWAS) which have identified regions of the human genome associated with mental disorders (such as schizophrenia and bipolar disorder). We seek to build on this progress by studying the identified genes as well as the effect of treatments at the RNA level. More specifically, questions that we seek to answer, include:

• What is the general nature of the disruption in gene expression in patients? Is the dysregulated state of an associated gene (and its consequences) independent of other associated genes, or is there an inter-dependence between associated genes?
• What are the molecular mechanisms through which current treatments act (mood stabilisers, anti-psychotics)?
• ANK3 is a gene for which there is strong genomic evidence of an association with bipolar disorder. Which molecular and cellular functions of ANK3 are disrupted in bipolar disorder?

New direction: the influence of the immune system on the brain
Research increasingly points to immunological factors playing a role in neurological and neuro-psychiatric disorders. I have recently published studies on the role of the complement system and defensins in mental disorders, and am currently performing a large study on the connection between calvarial bone marrow adiposity and pathologies of other organs, including the brain.

Collaborations with the clinical section: monogenic disorders
The majority of the patients referred to our department suffer from monogenic congenital disease. I have contributed HTS expertise to several projects employing exome and whole genome sequencing to identify the causal variant for patient cases that could not be solved by traditional means. Further, I have contributed to the development of a computational platform for the storage of sensitive human data that is now used by many medical departments across Norway and by our department for the analysis of all diagnostic samples that are sequenced using high throughput methods. I also participate in the acquisition of new technology for later transfer to the clinical and diagnostic sections, as exemplified by recent work where we verified putative mosaic variants by droplet digital PCR (ddPCR) in a cohort of patients with segmental overgrowth syndrome.

Expertise
My technical expertise is primarily in the analysis of genomic and transcriptomic data and, in particular, high throughput sequencing (HTS) data (DNAseq, RNAseq, ChIPseq). I built up this expertise between 2009 and 2013 while working at the Norwegian Sequencing Center and the Department of Medical Genetics. I have taught two HTS analysis courses to MSc and PhD students at the University of Oslo since 2012. Further, I have been the supervisor of 2 PhD students (as co-supervisor) and I am currently supervising a PhD student (as main supervisor) as well as two post-doctoral fellows.

Techniques and methods 
- Computational biology
- High-throughput sequencing and its analysis: DNAseq, ChIPseq, and particularly RNAseq.
- Digital droplet PCR (ddPCR)