Helen Miranda Knight studied Natural Science as an undergraduate and did a M.Sc. in Neuroscience at Edinburgh University working in the in the labs of Douglas Blackwood and Richard Morris. She then completed a PhD in Psychiatric Genetics at the IGMM in Edinburgh. After holding post-doctoral positions under Trevor Robbins and Barbara Sahakian at the Behavioral and Clinical Neuroscience Institute (BCNI), Cambridge University, and Chris Ponting at MRC Functional Genomics Unit (FGU/DPAG), Oxford University, in 2013 she came to Nottingham University to start her own group. Her lab investigates the genetics and epigenetic processes contributing to neurodevelopmental and cognitive disorders.
Since 2020 an elected member of the UoN Senate.
Currently an elected Senate member of the UoN Knowledge Exchange University Committee.
Genetic Society Ambassador, UoN https://genetics.org.uk/
Dr Knights' teaching interests are in human genetics and epigenomics of brain and neurological disorders.
Undergraduate and postgraduate teaching
Bachelor of Medical Sciences(BMedSci)
MSc Molecular genetics and Diagnostics: Molecular Services in Health Care; Molecular Basis of Genetic Disorders; Molecular Technologies;
BSc/MSci Natural Sciences
Convener for the following courses
MSc Molecular genetics and Diagnostics: Molecular Services in Health Care
MSc Molecular genetics and Diagnostics: Molecular Basis of Genetic Disorders
Research project supervision
Bachelor of Medical Sciences(BMedSci)
MSc Molecular genetics and Diagnostics
Tutor for MSc Molecular genetics and Diagnostics and BSc/MSci Natural Sciences
My research is focused on investigating the genetic and epigenetic basis of brain diseases and cognitive traits. We use the latest approaches, such as next generation sequencing technologies and… read more
FLITTON, MILES, RIELLY, NICHOLAS, WARMAN, RHIAN, WARDEN, DONALD, SMITH, A. DAVID, MACDONALD, IAN A. and KNIGHT, HELEN MIRANDA, 2019. Interaction of nutrition and genetics via DNMT3L-mediated DNA methylation determines cognitive decline NEUROBIOLOGY OF AGING. 78, 64-73 KNIGHT, H.M., PICKARD, B.S., MACLEAN, A., MALLOY, M.P., SOARES, D.C., MCRAE, A.F., CONDIE, A., WHITE, A., HAWKINS, W., MCGHEE, K., VAN BECK, M., MACINTYRE, D.J., STARR, J.M., DEARY, I.J., VISSCHER, P.M., PORTEOUS, D.J., CANNON, R.E., ST CLAIR, D., MUIR ,W.J. and BLACKWOOD, D.H.R., 2009. A cytogenetic abnormality and rare coding variants identify ABCA13 as a candidate gene in schizophrenia, bipolar disorder, and depression American Journal of Human Genetics. 85(6), 833-846
PICKARD, B.S., KNIGHT, H.M., HAMILTON, R.S., SOARES, D.C., WALKER, R., BOYD, J.K.F., MACHELL, J., MACLEAN, A., MCGHEE, K.A., CONDIE, A., PORTEOUS, D.J., ST. CLAIR, D., DAVIS, I., BLACKWOOD, D.H.R. and MUIR, W.J., 2008. A common variant in the 3'UTR of the GRIK4 glutamate receptor gene affects transcript abundance and protects against bipolar disorder Proceedings of the National Academy of Sciences. 105(39), 14940-14945
My research is focused on investigating the genetic and epigenetic basis of brain diseases and cognitive traits. We use the latest approaches, such as next generation sequencing technologies and advanced microscopy, to ask questions concerning what kind of genetic mutations, biological pathways and common mechanisms underlie susceptibility to disease and variation in cognitive ability.
Rare coding variants and genetic architecture of complex disease
Example study: ABCA13 ATP-binding cassette sub-family A member 13
A patient with schizophrenia was found to have a chromosomal abnormality which directly disrupted one gene, ABCA13, a lipid membrane transporter protein. Through exon sequencing of the functional domains of ABCA13, multiple rare coding variants were identified. Follow-up pedigree and case-control association studies strongly suggest that mutations within this gene, significantly contribute to the genetic aetiology of schizophrenia, bipolar disorder and major depression. This work raises key questions into the type of mutations underlying complex disease, for example; the frequency of rare risk variants (private to a family, ultra rarer, or 1-2%), whether carrying 2 or more rare coding variants (compound heterozygotes) is a feature of risk burden, and how common it is to have variants that contribute to several disorders which cross diagnostic categories.
ABCA13 cytogenetic lesion and rare coding variants in families with Schizophrenia, bipolar disorder and major depression
Regulatory mechanisms of risk variants and potential biological pathways
Example study: GRIK4 glutamate ionotropic kainite receptor 4 subunit
A deletion within the 3' untranslated region of the GRIK4 gene was identified as a protective factor for bipolar disorder. RNA secondary structure analysis in conjunction with evidence of increased relative mRNA abundance of the protective deletion allele suggested that this common variant may have a functional impact through differential mRNA stability. Using immunohistochemistry, GRIK4/KA1 protein expression was characterized in key regions of human brain and a genotype/protein expression correlation study indicated that KA1 expression was significantly increased in subjects carrying the protective allele. Expression patterns of KA1/GRIK4 support that three biological processes -adult hippocampal neurogenesis, HPA axis/stress activation and plasticity processes affecting neuronal circuitry- may putatively underlie this protective disease effect.
GRIK4/KA1 expression in the granular cell layer and molecular layer of the dentate gyrus, hilus, and CA4 field of the human hippocampus
Bioinformatics investigation of genomic features providing evidence that disease risk alleles may have functional non-coding effects
Genome wide case-control association studies and population/pedigree next generation re-sequencing studies frequently give rise to results implicating regions or single nucleotide polymorphisms (SNPs) which are not in coding regions of genes, (i.e. they are intronic or intergenic) but are potentially associated/linked with a trait or disease. How do we interpret these non-coding signals? And how do we tell if common SNPs are directly contributing to a phenotype or are merely associated through being near a causative variant (synthetic association)? One method currently used is to examine whether the variants are located within or/and directly disrupt regulatory elements and thus could have a functional non-coding effect. This involves bioinformatic data mining of functional genomic datasets for regulatory features such DNA methylation, histone marks and open chromatin markers.
SNPs associated with Alzheimer's disease and changes in cognitive ability located within the APOE and TOMM40 locus are indicated to have functional non-coding effects
Biomarkers for early Alzheimer's disease and cognitive decline through cohort/population studies
- Molecular and cognitive biomarkers for early dementia, cognitive decline and psychiatric disease endophenotypes.
- Epidemiology studies of cohorts to examine environmental factors which may contribute to risk or be protective (buffer) individuals from developing conditions.
Biomarkers of the early stages of brain disorders such as Alzheimer's disease
Current and future research includes epigenomic transcriptional regulation of synaptic function and contribution to brain disease processes.