Sheffield Institute for
Translational Neuroscience

Dr Tatyana Shelkovnikova PhD

MND Association Senior Non-Clinical Fellow


Research Interests

My group aims to provide insights into molecular underpinnings of RNP granule biology and their connection to human disease. Our overarching goals are:

  • to establish how altered composition and metabolism of the two types of RNP granules, stress granules and paraspeckles, contribute to the pathogenesis of ALS and frontotemporal dementia (FTD);
  • to discover and validate druggable targets for these devastating and currently incurable conditions;
  • to identify novel chemical probes for modulation of RNAs and RNP complexes.

Current Projects

  1. Regulation of RNP granules paraspeckles and stress granules under acute and chronic stress and in disease states (cellular models) - currently funded by the MND Association and BBSRC.
  2. The role of RNA-binding proteins FUS and TDP-43 in ALS and FTD (cellular and mouse models; analysis in human post-mortem tissue).
  3. Therapeutic targeting of RNA and RNA-protein complexes (assay development and screening activities).

Publications

  1. An H, Rabesahala de Meritens C, Shelkovnikova TA* (2021) Connecting the dots: RNA granule network in health and disease. Biochem Biophys Acta. 1868(8).119058. Invited review.
  2. Matsukawa K, Kukharsky MK, Park SK, Park S, Watanabe N, Iwatsubo T, Hashimoto T, Liebman SW, Shelkovnikova TA* (2021) Long non-coding RNA NEAT1_1 ameliorates TDP-43 toxicity in in vivo models of TDP-43 proteinopathy. RNA Biology. 10.1080/15476286.2020.1860580
  3. Kukharsky MK, Ninkina NN, An H, Telezhkin V, Wei W, Rabesahala de Meritens C, Cooper-Knock J, Nakagawa S, Hirose T, Buchman VL, Shelkovnikova TA* (2020) Long non-coding RNA Neat1 mediates adaptive behavioural response to stress in mice. Translational Psychiatry. 10:171.
  4. An H, Rabesahala de Meritens C, Buchman VL, Shelkovnikova TA* (2020) Frameshift peptides alter the properties of truncated FUS proteins in ALS-FUS. Molecular Brain. 13:77.
  5. An H, Tan J.-T., Shelkovnikova TA* (2019) Stress granules regulate stress-induced paraspeckle assembly. Journal of Cell Biology. 218(12):4127-414.
  6. Shelkovnikova TA*, An H, Skelt L, Tregoning JS, Humphreys IR, Buchman VL* (2019) Antiviral Immune Response as a Trigger of FUS Proteinopathy in Amyotrophic Lateral Sclerosis. Cell Reports. 29(13):4496-4508.e4.
  7. An H, Skelt L, Notaro A, Highley JR, Fox AH, La Bella V, Buchman VL*, Shelkovnikova TA* (2019) ALS-linked FUS mutations confer loss and gain of function in the nucleus by promoting excessive formation of dysfunctional paraspeckles. Acta Neuropathol Communications. 7(1):7.
  8. An H, Williams NG, Shelkovnikova TA* (2018) NEAT1 and paraspeckles in neurodegenerative diseases: A missing lnc found? Noncoding RNA Res. 3(4):243-252. Invited review
  9. Shelkovnikova TA*, An H, Kukharsky M, Dimasi P, Alexeeva S, Shabir O, Heath PR and Buchman VL (2018) Protective paraspeckle hyper-assembly downstream

Professional Activities

Regularly solicited to review grant applications and manuscripts.

Grants: MND Association; MRC; BBSRC; Strasbourg Institute for Advanced Studies (USIAS); Worldwide Cancer Research; French National Research Agency (ANR); Research Foundation Flanders’ (FWO); Israel Science Foundation; French Research Association on ALS; European Science Foundation.

Papers: reviewed for >20 journals, including Nat Neurosci, Nat Commun; Trends Genet; J Cell Biol, EMBO Rep, Cell Rep. >35 papers, for full list– see Publons.

Acted as external PhD examiner for students at the University College London / Crick Institute, London, UK and King’s College London.

Invited to speak at multiple departmental seminars (including UCL, universities at Australia, Japan, Italy, Russia) and conferences.

Participated in outreach events and patient-oriented activities, including demonstration at science festivals and MND guest research blog writing.

Biography

After graduating with an MSc degree in Genetics in 2008, I pursued a PhD in Biochemistry (both while in Russian Federation) which I completed in 2012. During my PhD training, supported by an EMBO fellowship, I contributed to the generation and characterisation of a unique mouse model of a fatal neurodegenerative disease, amyotrophic lateral sclerosis (ALS); report on this mouse model published in J Biol Chem was selected as Paper of the Year. I continued to develop this stream of research during my postdoctoral training at Cardiff University (Prof Buchman’s lab), where I spearheaded a number of projects focussing on (dys)metabolism of ribonucleoprotein (RNP) granules in ALS. In 2015, these studies were supported by a 3-year fellowship from the Medical Research Foundation. In 2018, I was awarded a 4-year senior non-clinical fellowship from the MND Association to start my own group at the Medicines Discovery Institute, a newly established Cardiff University’s translational unit. Since then, my research was also supported by the AMS Springboard award, the ISSF Translational Kick-Start award, a Welsh Government drug discovery grant and more recently, a research grant from the BBSRC. In September 2021, I moved to SITraN, University of Sheffield, to continue studies into the molecular pathogenesis of ALS and related disorders within a world-leading centre for neurodegenerative disease research.

Awards

  • European Network for the Cure of ALS (ENCALS) Young Investigator Award 2020.
  • Featured in the Lifeline section of the Lancet Neurology journal.
  • First-author paper selected as Paper of the Year in the Journal of Biological Chemistry in 2013.
  • Best PhD student poster prize to Hayan An for the work under my supervision at ENCALS 2016.
  • Best oral talk, 9th Mammalian Genes, Development and Disease Meeting (2015).
  • Best poster, Gordon Research Conference ‘Neurobiology of Brain Disorders’ (2014).
  • Best poster, 1st International Symposium on Stress-Associated RNA Granules in Human Disease and Viral Infection (2014).
  • Best poster prize as part of Young Investigators program at 8th IBRO World Congress of Neuroscience (2011).

Teaching Interests

I contribute to teaching of laboratory-based undergraduate (final year) and postgraduate (MSc) students.

Contact Details

Department of Neuroscience
SITraN
University of Sheffield
385a Glossop Road
Sheffield
S10 2HQ

+44 (0)114 2222270
t.shelkovnikova@sheffield.ac.uk