Development of quantitative imaging biomarkers for characterization of neural functional abnormalities in preclinical models of neurodevelopmental disorders.

Description

Applications should be made to the project supervisor, Harish Poptani (harishp@liverpool.ac.uk), in the first instance via CV and cover letter.

Candidates will be invited to interview with UoL and NIMHANS.  Both Parties must approve the admission, in line with the terms of the Dual PhD Programme.

The successful candidate should then submit a formal application through the University online application form https://www.liverpool.ac.uk/study/postgraduate-research/how-to-apply/

Please specify on your application that you are applying for the NIMHANS Dual PhD Programme.

 

Start date will be determined after formal approval from both partners and in consideration of the NIMHANS Dual PhD Agreement. 

 

Project Description:

This multi-institutional Dual PhD project between the University of Liverpool and the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India. The project aims to develop quantitative magnetic resonance imaging and spectroscopic imaging biomarkers to assess abnormalities in neural function and metabolism in well-established preclinical models of neurological disorders. Specifically, the project will initially develop and validate longitudinal diffusion tensor tractography and MR spectroscopy in a Trappc9 knockout model of intellectual disability, which demonstrates microcephaly and learning disabilities (https://pubmed.ncbi.nlm.nih.gov/38331351/). Once established, these makers will be evaluated in other animal models including models of autism spectrum disorders and stress due to early maternal separation and isolation.

 

Training

The project will provide training in several strategic areas including quantitative skills in neuroimaging, metabolism, behavioural biology and experimental design involving animals. In addition, interdisciplinary skills such as preclinical imaging, genotyping, behaviour assays, histology and immunohistochemistry will also be provided by the supervisory team.

Applicants must have a Master’s degree in either biomedical sciences, bioengineering or a relevant field. Due to funding restrictions, only UK citizens or residents with permanent residency in UK are eligible to apply (applicants must be classed as HOME for fee purposes).

The successful candidate will commit to spending up to two years at the University of Liverpool and up to two years at NIMHANS in Bengaluru (India). The expected pattern of study for this studentship is Year 1 and Year 2 based in Liverpool and Year 3 and Year 4 based in India.

Availability

Open to UK applicants

Funding information

Funded studentship

Funded by the Pratiksha Trust this four-year Dual PhD Programme between the University of Liverpool and the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, India, will provide a PhD award from both institutions. Funding will cover stipend at the UKRI level, tuition fees (Home rate only), research support fees and travel costs.

Supervisors

References

Professor Harish Poptani – expertise in development of novel imaging biomarkers in animal models of disease including cancer and neurodevelopment disorders

  1. Aljuraysi S, Platt M, Pulix M, Poptani H, Plagge A. Microcephaly with a disproportionate hippocampal reduction, stem cell loss and neuronal lipid droplet symptoms in Trappc9 KO mice. Neurobiol Dis. 2024 Mar:192:106431. doi: 10.1016/j.nbd.2024.106431. 
  2. Llambrich S, Tielemans B, Saliën E, Atzori M, Wouters K, Van Bulck V, Platt M, Vanherp L, Gallego Fernandez N, Grau de la Fuente L, Poptani H, Verlinden L, Himmelreich U, Croitor A, Attanasio C, Callaerts-Vegh Z, Gsell W, Martínez-Abadías N, Vande Velde G. Pleiotropic effects of trisomy and pharmacologic modulation on structural, functional, molecular, and genetic systems in a Down syndrome mouse model. Elife2024 Mar 18:12:RP89763. doi: 10.7554/eLife.89763.
  3. M Kumar, JT Duda, WT Huang, C Kenworthy, R Ittyerah, S Pickup, ES Brodkin, JC Gee, T Abel, H Poptani. High resolution magnetic resonance imaging for characterization of the Neuroligin-3 knock-in mouse model associated with autism spectrum disorder. PLOS One 2014 Oct 9;9(10):e109872. doi: 10.1371/journal.pone.0109872. eCollection 2014.

 

Dr Antonius Plagge – expertise in the generation and analysis of genetically modified mouse models of neurobiological disorders using behavioural, histological, molecular and cell-biological techniques.

  1. Aljuraysi S, Platt M, Pulix M, Poptani H, Plagge A. Microcephaly with a disproportionate hippocampal reduction, stem cell loss and neuronal lipid droplet symptoms in Trappc9 KO mice. Neurobiol Dis. 2024 Mar:192:106431. doi: 10.1016/j.nbd.2024.106431. Epub 2024 Feb 7.
  2. Mousavinejad M, Skidmore S, Barone FG, Tyers P, Pisupati V, Poptani H, Plagge A, Barker RA, Murray P, Taylor A, Hill CJ. Assessing human embryonic stem cell-derived dopaminergic neuron progenitor transplants using non-invasive imaging techniques. Mol Imaging Biol. 2020 Oct;22(5):1244-1254. doi: 10.1007/s11307-020-01499-4.
  3. Comenge J, Sharkey J, Fragueiro O, Wilm B, Brust M, Murray P, Lévy R, Plagge A. Multimodal cell tracking from systemic administration to tumour growth by combining gold nanorods and reporter genes. Elife. 2018 Jun 27;7:e33140. doi: 10.7554/eLife.33140.

 

Dr Manoj Kumar - Expertise in development of quantitative neuroimaging methods for early and accurate characterization of various pathological conditions in preclinical (animal models), as well as in humans.

  1. Kumar M, Kim S, Pickup S, Chen R, Fairless AH, Ittyerah R, Abel T, Brodkin ES, Poptani H. Longitudinal in-vivo diffusion tensor imaging for assessing brain developmental changes in BALB/cJ mice, a model of reduced sociability relevant to autism. Brain Res. 2012 May 21;1455:56-67. doi: 10.1016/j.brainres.2012.03.041. Epub 2012 Mar 25. PMID: 22513103; PMCID: PMC3340503.
  2. Kumar VJ, Grissom NM, McKee SE, Schoch H, Bowman N, Havekes R, Kumar M, Pickup S, Poptani H, Reyes TM, Hawrylycz M, Abel T, Nickl-Jockschat T. Linking spatial gene expression patterns to sex-specific brain structural changes on a mouse model of 16p11.2 hemideletion. Transl Psychiatry. 2018 May 29;8(1):109. doi: 10.1038/s41398-018-0157-z. PMID: 29844452; PMCID: PMC5974415.
  3. Kumar M, Hiremath C, Khokhar SK, Bansal E, Sagar KJV, Padmanabha H, Girimaji AS, Narayan S, Kishore MT, Yamini BK, Jac Fredo AR, Saini J, Bharath RD. Altered cerebellar lobular volumes correlate with clinical deficits in siblings and children with ASD: evidence from toddlers. J Transl Med. 2023 Apr 7;21(1):246. doi: 10.1186/s12967-023-04090-x. PMID: 37029372; PMCID: PMC10080978.

 

Professor Laxmi T Rao - Established several neurodevelopmental models – early life stress-induced nicotine addiction at adolescence age, fear cognition model, and autism spectrum disorders models using Sprague Dawley rats – to delineate the neurophysiological mechanisms of neurochemical and hormonal changes under varied behavioral functions.

  1. Shruthi S. Sharma, Doreswamy Yoganarasimha and Laxmi T.R. Characterization of neuronal oscillations in the prelimbic cortex, nucleus accumbens and CA1 hippocampus during object retrieval task in rats predisposed to early life stress. Behavioral and Brain Functions 2024 (in press).
  2. Chowdhury A, Shruthi S Sharma, Arjun B.S., Hardik J. Pandya, B.S. Shankaranarayana Rao, and T R. Laxmi, Risky Decision-taking Task: a novel paradigm to assess the risk-taking behaviour in rats predisposed to early life stress. Neuroscience Methods. Apr 18:109864 (2023). PMID: 37080434.
  3. Kumari Anshu, Ajay Kumar Nair, Shoba Srinath, Rao Laxmi, Altered developmental trajectory in male and female rats in a prenatal valproic acid exposure model of Autism Spectrum Disorder, J. Autism and Developmental Disorders 2023 Nov;53(11):4390-4411. doi: 10.1007/s10803-022-05684-y