People

Dr Sue Shackleton

Associate Professor

School/Department: Molecular Cell Biology, Department of

Telephone: +44 (0)116 229 7058

Email: ss115@leicester.ac.uk

Profile

I gained my degree in Biochemistry at the University of Oxford and remained there to study for a DPhil in Clinical Medicine focusing on the genetics of cystic fibrosis. This work sparked my interest in inherited disorders and understanding how small changes in the human genome cause protein dysfunction and result in the myriad of disorders that occur in human populations. I undertook postdoctoral work studying the mechanism of internalisation of the insulin receptor in Geneva. In my second postdoctoral position at the University of Leicester I returned to the field of medical genetics successfully identifying the LMNA gene as causative of familial partial lipodystrophy. This discovery formed the foundation of my subsequent research career in which I have studied proteins of the nuclear envelope, their roles in nuclear function and involvement in rare inherited disorders. I am currently the Programme Director for the Biochemistry and Medical Biochemistry degree streams and responsible for co-ordinating the teaching across these programmes as well as contributing to the management and development of teaching across the School of Biological Sciences. 

Research

My research in recent years has focused on the connections between the cell nucleus and its surrounding cytoskeleton. A protein complex termed the LINC complex, which spans the double membrane of the nucleus, is central to these connections. The LINC complex is crucial for maintaining cell mechanical stability, transmitting mechanical signals from the cell surfaced to the nucleus and for correct movement and positioning of nuclei within the cytoplasm. My lab has been involved in studying the function of the LINC complex and its role in controlling nuclear positioning in muscle through recruitment of a microtubule organising centre and microtubule motor proteins, defects in which contribute to muscle disorders such as Emery-Dreifuss muscular dystrophy.

Publications

1. Colon-Bolea P, Garcia-Gomez R, Shackleton S, Crespo P, Bustelo XR, Casar B. RAC1 induces nuclear alterations through the LINC complex to enhance melanoma invasiveness. (2020) Molecular Biology of the Cell, 31, 2768-2778. DOI: 10.1091/mbc.E20-02-0127. 
2. Gimpel P, Lee YL, Sobota RM, Calvi A, Koullourou V, Patel R, Mamchaoui K, Nedelec F, Shackleton S, Schmoranzer J, Burke B, Cadot B, Gomes ER. Nesprin-1alpha-Dependent Microtubule Nucleation from the Nuclear Envelope via Akap450 Is Necessary for Nuclear Positioning in Muscle Cells (2017) Current Biology, 27, 2999-3009. DOI: 10.1016/j.cub.2017.08.031
3. Zhou, C., Li, C., Zhou, B., Sun, H., Koullourou, V., Holt, I., Puckelwartz, M.J., Warren, D.T., Hayward, R., Lin, Z., Zhang, L., Morris, G.E., McNally, E.M., Shackleton, S., Rao, L., Shanahan, C.M., Zhang, Q. Novel nesprin-1 mutations associated with dilated cardiomyopathy cause nuclear envelope disruption and defects in myogenesis. (2017) Human Molecular Genetics, 26, 2258-2276. DOI: 10.1093/hmg/ddx116.
4. Mikolcevic, P., Isoda, M., Shibuya, H., del Barco Barrantes, I., Igea, A., Suja, J. A., Shackleton, S., Watanabe, Y. and Nebreda, A. R. Essential role of the atypical Cdk2 activator RingoA in meiotic telomere tethering to the nuclear envelope. (2016) Nature Communications, 7, 11084. 
5. Patel JT., Bottrill A., Prosser S.L., Jayaraman S., Straatman K., Fry A.M., Shackleton S. Mitotic phosphorylation of SUN1 loosens its connection with the nuclear lamina while the LINC complex remains intact. (2014) Nucleus 5, 462-473.
6. Meinke, P., Mattioli, E., Haque, F., Antoku, S., Columbaro, M., Straatman, K.R., Worman, H.J., Gundersen, G.G., Lattanzi, G., Wehnert, M., Shackleton, S. Muscular Dystrophy-Associated SUN1 and SUN2 Variants Disrupt Nuclear-Cytoskeletal Connections and Myonuclear Organization. (2014) PLoS Genetics 10, e1004605.
7. Watkins, R.J., Patil, R., Goult, B.T., Thomas, M.G., Gottlob, I. and Shackleton, S. A novel interaction between FRMD7 and CASK - evidence for a causal role in idiopathic infantile nystagmus. (2013) Human Molecular Genetics 22, 2105-2118. 
8. Haque F, Mazzeo, D., Patel, J.T., Smallwood, D.T., Ellis, J.A., Shannahan, C.M. and Shackleton, S. Mammalian SUN protein networks at the inner nuclear membrane and their role in laminopathy disease processes. (2010) Journal of Biological Chemistry 285, 3487-98. 
9. Haque, F., Lloyd, D, Smallwood, D., Dent, C., Shanahan, C., Fry, A., Trembath, R. and Shackleton, S. SUN1 interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton (2006) Molecular and Cellular Biology 26, 3738-3751. 
10. Shackleton, S., Lloyd, D., Jackson, S., Evans, R., Niermeijer, M., Singh, B., Schmidt, H., Brabant, G., Kumar, S., Durrington, P., Gregory, S., O'Rahilly, S., Trembath, R. The LMNA gene encoding lamin A/C is mutated in partial lipodystrophy (2000) Nature Genetics 24, 152-156. 

 

Supervision

Current projects in my lab centre around the understanding of formation of the nuclear microtubule organising centre during muscle development the role that the nesprin-1alpha2 LINC complex plays in this process and how defects in these processes may be impacted in inherited muscle disorders.

Teaching

I teach on a range of biochemistry, cell biology and medically-oriented modules across all three years of the Biological Sciences degree programmes.

Press and media

Inherited diseases of the nuclear envelope.

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