Starter Grants for Clinical Lecturers awardee

University of Cambridge (previously at Newcastle University)

Identification of new disease genes in combined respiratory chain deficiencies

To celebrate the 10 year anniversary of the Starter Grants for Clinical Lecturers scheme we are pleased to feature case studies of past and present Starter Grant awardees. Professor Rita Horvath was awarded a Starter Grant for Clinical Lecturers in 2009, and tells us here how the award was important in helping her establish her own translational research group. She also highlights some of the main achievements and challenges of her research career.  

Can you give us an overview of your research interests?

I am a neurologist specialising in rare neurogenetic disorders. The focus of my research over the past 20 years has primarily been mitochondrial diseases, but I have also developed a new clinical and research programme in inherited peripheral neuropathies and other rare genetic and metabolic neurological diseases.

I played a key role in the identification of 11 novel disease genes in severe childhood onset conditions and characterised, clinically and biochemically, a large cohort of patients with multiple respiratory chain enzyme deficiency. I identified the cause and molecular mechanism of reversible infantile mitochondrial disease and showed that altered thio-modification of mitochondrial tRNAs may underlie the presentation, suggesting that tRNA modification may be manipulated as a novel target to develop therapies in mitochondrial disease.

What was the impact of your Starter Grant?

My study focussed on the identification of gene defects in children with combined respiratory chain deficiency. With the funding, I successfully established methods of studying mitochondrial translation and coenzyme Q10 metabolism, identified a number of new genes and detected mutations in recently reported disease genes causing a defect of mitochondrial translation or coenzyme Q10 biosynthesis. My research enabled some effective treatments for patients.

The Starter Grant enabled me to start my own laboratory and to optimally combine clinical and laboratory work, underpinned by successful translational research grant and personal investigator awards.

What are the challenges you face as a clinical academic?

I find that combining clinical commitments and laboratory research is challenging, however being a clinician allows me to better define important research questions with more implications for patients. I find it very appealing that if I identify a potential treatment in the laboratory, as a clinical academic, I could bring it forward to clinical trials.

What’s next for you and your research?

After the Starter Grant I was able to develop my research area and expertise in Newcastle, but recently I felt that I needed a new challenge. Therefore, I have now accepted the post of the Director of Research at the University of Cambridge. The extremely high quality of basic science at the Department of Neurosciences and Mitochondrial Biology Unit and the proximity of large national cohorts will help to enrich my research trajectory.

Research highlights 

• Professor of Neurogenetics, Newcastle University, in 2013

• Director of Research, University Of Cambridge, in 2018

• Chief Investigator of an international clinical trial

• Chair of the mitochondrial disease group within the European Reference Network on Rare Neuromuscular Diseases (ERN-NMD)