Thomas Suslak PhD

Thomas Suslak


Research Interests

My research is primarily focused on mechanosensation. I am interested in understanding the mechanisms by which stretch-sensitive endings transduce mechanical stimuli to electrical signals, transmitted to the CNS. The field of mechanosensation has attracted a lot of attention in recent years but so far the underlying mechanisms at the molecular level are poorly understood. Using techniques in electrophysiology, alongside mathematical modelling, I aim to promote deeper insight into the interactions that occur in order to effect mechanotransduction and identify the mechanisms involved using additional techniques in immunohistochemistry and genetics.

Publications:
2015
  Stretching the imagination beyond muscle spindles - stretch-sensitive mechanisms in arthropods
Suslak, TJ & Jarman, AP 2015, 'Stretching the imagination beyond muscle spindles - stretch-sensitive mechanisms in arthropods' Journal of Anatomy. DOI: 10.1111/joa.12329

Much attention has been given to mammalian muscle spindles and their role in stretch-mediated muscle proprioception. Recent studies, particularly, have sought to determine the molecular mediators of stretch-evoked mechanotransduction, which these endings rely upon for functionality. Nonetheless, much about these endings remains unknown. Opportunities may be presented from consideration of extensive parallel research in stretch receptor mechanisms in arthropods. Such systems may provide a useful source of additional data and powerful tools for dissecting the complex systems of stretch transduction apparatus. At the least, such systems provide tractable exemplars of how organisms solve the problem of converting stretch stimuli to electrical output. Potentially, they may even provide molecular mechanisms and candidate molecular mediators of direct relevance to mammalian muscle spindles. Here we provide a brief overview of research on arthropod stretch receptors.


General Information
Organisations: Edinburgh Neuroscience.
Authors: Suslak, Thomas J & Jarman, Andrew P.
Publication Date: 16 Jun 2015
Publication Information
Category: Article
Journal: Journal of Anatomy
ISSN: 0021-8782
Original Language: English
DOIs: 10.1111/joa.12329
  Piezo is essential for amiloride-sensitive stretch-activated mechanotransduction in larval Drosophila dorsal bipolar dendritic sensory neurons
Suslak, T, Watson, S, Thompson, KJ, Shenton, FC, Bewick, GS, Armstrong, JD & Jarman, AP 2015, 'Piezo is essential for amiloride-sensitive stretch-activated mechanotransduction in larval Drosophila dorsal bipolar dendritic sensory neurons' PLoS One, vol 10, no. 7, e0130969.
Stretch-activated afferent neurons, such as those of mammalian muscle spindles, are essential for proprioception and motor co-ordination, but the underlying mechanisms of mechanotransduction are poorly understood. The dorsal bipolar dendritic (dbd) sensory neurons are putative stretch receptors in the Drosophila larval body wall. We have developed an in vivo protocol to obtain receptor potential recordings from intact dbd neurons in response to stretch. Receptor potential changes in dbd neurons in response to stretch showed a complex, dynamic profile with similar characteristics to those previously observed for mammalian muscle spindles. These profiles were reproduced by a general in silico model of stretch-activated neurons. This in silico model predicts an essential role for a mechanosensory cation channel (MSC) in all aspects of receptor potential generation. Using pharmacological and genetic techniques, we identified the putative mechanosensory channel, DmPiezo, as a strong candidate for this functional role in dbd neurons, with TRPA1 playing a subsidiary role. We also show that rat muscle spindles exhibit a ruthenium red-sensitive current, but found no expression evidence this corresponds to Piezo activity. In summary, we show that the dbd neuron is a stretch receptor and demonstrate that this neuron is a tractable model for investigating mechanisms of mechanotransduction.
General Information
Organisations: Edinburgh Neuroscience.
Authors: Suslak, Thomas, Watson, Sonia, Thompson, Karen J., Shenton, Fiona C., Bewick, Guy S., Armstrong, J. Douglas & Jarman, Andrew P..
Number of pages: 16
Publication Date: Jul 2015
Publication Information
Category: Article
Journal: PLoS One
Volume: 10
Issue number: 7
ISSN: 1932-6203
Original Language: English
2013
  Modelling mechanotransduction in primary sensory endings
Suslak, T, McKay-Fletcher, JA, Armstrong, D, Jarman, A & Bewick, G 2013, 'Modelling mechanotransduction in primary sensory endings' Neuroinformatics 2013 6th INCF Congress, Stockholm, Sweden, 27/08/13 - 29/08/13, .
Mechanotransduction is a process fundamental to life. It underpins a variety of sensory modalities from hearing to blood pressure regulation. However, the molecular components of the mechanosensory mechanisms in primary sensory endings are poorly understood. Experimental approaches to solving this problem are long and laborious. Therefore, a theoretical approach was proposed as an efficient means to circumventing this process. A mathematical, biophysical model of mechanosensory endings was implemented, which reproduced existing experimental data of the receptor potential of the mammalian muscle spindle primary ending. This probabilistic model combines mathematical representations of different ion channel types to produce an output which is the predicted receptor potential of the sensory ending, given the presence of specific ion channels. The model outputs the tension-dependent electrical response of the receptor, given a stretch stimulus. The parameters required for this model identify the necessary molecular entities required for this behaviour to occur. The dbd (dorsal bipolar dendritic) neuron in D. melanogaster larvae fulfils a similar role to the muscle spindle in mammals. Electrophysiological data was obtained from these neurons via whole-cell patching. It was shown that the dbd neuron can respond to both electrical and mechanical stimuli, but that these responses are noticeably distinct. Furthermore the stretch-evoked data obtained from these receptors was equivalent to that predicted by the model, demonstrating a cross-taxa correlation between the behaviour of neurons in this class. This finding enables simple genetic assays to be carried out in D. melanogaster to ascertain the identity of molecules which are involved in primary mechanotransduction at the sensory terminal. A simple bioinformatics search has yielded a shortlist of candidates which fulfill the criteria of the model predictions. These can now be experimentally tested in a simple and direct approach.
General Information
Organisations: Centre for Integrative Physiology.
Authors: Suslak, Thomas, McKay-Fletcher, Jack Alexander, Armstrong, Douglas, Jarman, Andrew & Bewick, Guy.
Publication Date: 2013
Publication Information
Category: Poster
Original Language: English
  A model of mechanotransduction in Drosophila non-ciliated, primary endings
Suslak, T, Bewick, G, Armstrong, D & Jarman, A 2013, 'A model of mechanotransduction in Drosophila non-ciliated, primary endings' Physiology 2013 (IUPS), Birmingham, United Kingdom, 21/07/13 - 26/07/13, .
Mechanotransduction is a process fundamental to life. It underpins a variety of sensory modalities from hearing to blood pressure regulation. However, the molecular components of the mechanosensory mechanisms in primary sensory endings are poorly understood. Experimental approaches to solving this problem are long and laborious. Therefore, a theoretical approach was proposed as an efficient means to circumventing this process. A mathematical, biophysical model of mechanosensory endings was implemented, which reproduced existing experimental data of the receptor potential of the mammalian muscle spindle primary ending. This probabilistic model combines mathematical representations of different ion channel types to produce an output which is the predicted receptor potential of the sensory ending, given the presence of specific ion channels. The model outputs the tension-dependent electrical response of the receptor, given a stretch stimulus. The parameters required for this model identify the necessary molecular entities required for this behaviour to occur. The dbd (dorsal bipolar dendritic) neuron in D. melanogaster larvae fulfils a similar role to the muscle spindle in mammals. Electrophysiological data was obtained from these neurons via whole-cell patching. It was shown that the dbd neuron can respond to both electrical and mechanical stimuli, but that these responses are noticeably distinct. Furthermore the stretch-evoked data obtained from these receptors was equivalent to that predicted by the model, demonstrating a cross-taxa correlation between the behaviour of neurons in this class. This finding enables simple genetic assays to be carried out in D. melanogaster to ascertain the identity of molecules which are involved in primary mechanotransduction at the sensory terminal. A simple bioinformatics search has yielded a shortlist of candidates which fulfil the criteria of the model predictions. These can now be experimentally tested in a simple and direct approach.
General Information
Organisations: Centre for Integrative Physiology.
Authors: Suslak, Thomas, Bewick, Guy, Armstrong, Douglas & Jarman, Andrew.
Publication Date: 2013
Publication Information
Category: Poster
Original Language: English
  A model of mechanotransduction in Drosophila non-ciliated, primary endings
Suslak, T, McKay-Fletcher, JA, Bewick, G, Armstrong, D & Jarman, A 2013, 'A model of mechanotransduction in Drosophila non-ciliated, primary endings' Neuroscience Day 2013, Edinburgh, United Kingdom, 20/03/13 - 20/03/13, .
Mechanotransduction is a process fundamental to life. It underpins a variety of sensory modalities from hearing to blood pressure regulation. However, the molecular components of the mechanosensory mechanisms in primary sensory endings are poorly understood. Experimental approaches to solving this problem are long and laborious. Therefore, a theoretical approach was proposed as an efficient means to circumventing this process. A mathematical, biophysical model of mechanosensory endings was implemented, which reproduced existing experimental data of the receptor potential of the mammalian muscle spindle primary ending. This probabilistic model combines mathematical representations of different ion channel types to produce an output which is the predicted receptor potential of the sensory ending, given the presence of specific ion channels. The model outputs the tension-dependent electrical response of the receptor, given a stretch stimulus. The parameters required for this model identify the necessary molecular entities required for this behaviour to occur. The dbd (dorsal bipolar dendritic) neuron in D. melanogaster larvae fulfils a similar role to the muscle spindle in mammals. Electrophysiological data was obtained from these neurons via whole-cell patching. It was shown that the dbd neuron can respond to both electrical and mechanical stimuli, but that these responses are noticeably distinct. Furthermore the stretch-evoked data obtained from these receptors was equivalent to that predicted by the model, demonstrating a cross-taxa correlation between the behaviour of neurons in this class. This finding enables simple genetic assays to be carried out in D. melanogaster to ascertain the identity of molecules which are involved in primary mechanotransduction at the sensory terminal. A simple bioinformatics search has yielded a shortlist of candidates which fulfil the criteria of the model predictions. These can now be experimentally tested in a simple and direct approach.
General Information
Organisations: Centre for Integrative Physiology.
Authors: Suslak, Thomas, McKay-Fletcher, Jack Alexander, Bewick, Guy, Armstrong, Douglas & Jarman, Andrew.
Publication Date: 2013
Publication Information
Category: Poster
Original Language: English
2012
  A general mathematical model of transduction events in mechanosensory stretch receptors
Suslak, T, Bewick, G, Armstrong, D & Jarman, A 2012, 'A general mathematical model of transduction events in mechanosensory stretch receptors' Physiology 2012, Edinburgh, United Kingdom, 2/07/12 - 5/07/12, .
Mechanoreceptors are the largest class of sensory neurons, expressing great diversity, and are implicated in a variety of sensory pathways, including touch, nociception, hearing and proprioception. However, of all the sensory modalities, the mechanisms of mechanosensation are the least understood. Focusing on non-ciliated, stretch-sensitive mechanoreceptors, and using experimental and theoretical approaches, a mathematical explanation of their function has been produced and tested in a model system.
It has been shown that a biomechanical model of mechanoreceptors is sufficient to describe the mode of activation and adaptation in type-II, non-ciliated, stretch-sensitive receptors. Whole-cell patch clamp recordings from dbd neurons of D. melanogaster have also successfully yielded data on the behaviour of these endings, which are consistent with the model predictions. Furthermore, the model has also been shown to be a valid representation of extant mammalian data.
The experimentally-derived data can be used to constrain the current model of mechanoreceptor adaptation. Subsequently, the parameters of this model can be used to identify the molecular mediators of mechanotransduction in our model system. Furthermore, these findings are likely to have significance in similar systems across taxa.
General Information
Organisations: Centre for Integrative Physiology.
Authors: Suslak, Thomas, Bewick, Guy, Armstrong, Douglas & Jarman, Andrew.
Publication Date: 2012
Publication Information
Category: Poster
Original Language: English
2011
  A general mathematical model of transduction events in mechano-sensory stretch receptors
Suslak, T, Armstrong, DJ & Jarman, A 2011, 'A general mathematical model of transduction events in mechano-sensory stretch receptors' 2nd Scottish Drosophila Research Conference, Dundee, United Kingdom, 9/12/11, .
General Information
Organisations: Centre for Integrative Physiology.
Authors: Suslak, Thomas, Armstrong, Douglas J. & Jarman, Andrew.
Publication Date: 2011
Publication Information
Category: Poster
Original Language: English
  A mathematical model of electrical transduction events in crayfish stretch receptors
Suslak, T, Jarman, A & Armstrong, D 2011, 'A mathematical model of electrical transduction events in crayfish stretch receptors'.
General Information
Organisations: Institute for Adaptive and Neural Computation .
Authors: Suslak, Thomas, Jarman, Andrew & Armstrong, Douglas.
Publication Date: 2011
Publication Information
Category: Poster
Original Language: English
  A general mathematical model of transduction events in mechano-sensory stretch receptors
Armstrong, JD, Jarman, AP & Suslak, T 2011, 'A general mathematical model of transduction events in mechano-sensory stretch receptors' Network: Computation in Neural Systems, vol 22, no. 1-4, pp. 133-42. DOI: 10.3109/0954898X.2011.638967
Crayfish (Astacus astacus) muscle stretch receptors show strong homology to mammalian muscle spindles and bipolar neurons in D. melanogaster. All are typical, non-ciliated, stretch-sensitive, afferent neurons. Such receptors are observed in many species and perform an important sensory role. However, they are poorly characterised. A previous study reported a bio-mechanical and behavioural model of A. astacus stretch receptors, which used the principles of elasticity and tension in a spring to describe the adaptation of a mechano-sensory ending. This model described the changing mechano-sensory currents in the receptor when subjected to a stretch protocol. Here, we re-implement and extend this model. Notably, we introduce additional descriptions of voltage-gated channels that are suggested to contribute to stretch receptor mechano-transduction. Our model presents a more complete picture of the initiation of the mechano-receptor potential in response to a stretching stimulus. The inclusion of voltage-dependent sodium and potassium currents in addition to the initial mechano-sensitive sodium current allowed the model to account for most of the initial stretch response of the receptor. This preliminary model has potential for extension to describe fully the behaviour of non-ciliated mechano-sensors across species and predict the molecular mediators of mechano-transduction.
General Information
Organisations: Neuroinformatics DTC.
Authors: Armstrong, J D, Jarman, A P & Suslak, Thomas.
Keywords: (Animals, Mechanoreceptors, Models, Theoretical, Sensory Receptor Cells, Signal Transduction. )
Number of pages: 10
Pages: 133-42
Publication Date: 2011
Publication Information
Category: Article
Journal: Network: Computation in Neural Systems
Volume: 22
Issue number: 1-4
ISSN: 0954-898X
Original Language: English
DOIs: 10.3109/0954898X.2011.638967

Projects:
Determining the mechanism of electrical transduction in nonciliated stretch receptors (PhD)