Detail

Keywords

Antidepressive Agents; Drosophila melanogaster; Epilepsy; Folding and targeting of neurotransmitter transporters and GPCRs; Genetic Variation; Intellectual Disability; Molecular Mechanisms of Pharmacological Action; Mutation, Missense; Neuropharmacology; Neuropharmacology; Neuropsychopharmacology; Neurotransmitter Transporters; Neurotransmitter Uptake Inhibitors; Parkinsonian Disorders; Protein Folding; Protein Trafficking

Research interests

Our research centers on rare disease variants in human neurotransmitter transporter genes and their role in neurological and neurodevelopmental disorders, including autism, epilepsy, infantile parkinsonism and intellectual disability. We combine functional analyses with detailed molecular investigations, focusing on disrupted protein folding and trafficking mechanisms.

A key objective of our work is therapeutic innovation. Using cellular systems and Drosophila models, we explore pharmacological rescue strategies based on small molecules such as chemical chaperones and allosteric modulators. Additionally, we perform structure-activity relationship studies on monoamine transporters, advancing our understanding of how antidepressants and psychostimulants interact with their molecular targets.

Techniques, methods & infrastructure

Our laboratory integrates advanced pharmacological, molecular, cellular and imaging techniques to investigate the regulation and function of SLC6 transporters. Pharmacological approaches include radioligand uptake and binding assays, as well as efflux and superfusion experiments, enabling detailed characterisation of transporter activity, substrate specificity and inhibitor pharmacodynamics. Molecular biology and biochemical techniques encompass site-directed mutagenesis for structure–function analyses, DNA and RNA purification, cell surface biotinylation to assess membrane trafficking and protein detection methods such as immunoblotting and immunocytochemistry. Cell culture methodologies involve the use of primary neuronal cultures and established cell lines, alongside transient and stable transfection systems. Gene function is further dissected using siRNA-mediated knockdown approaches and related gene-silencing strategies. Advanced imaging techniques include confocal laser scanning microscopy and Förster resonance energy transfer (FRET) to study protein localisation, interactions and conformational dynamics in living cells. In addition, we employ Drosophila melanogaster as an in vivo model system to investigate the physiological roles and regulatory mechanisms of SLC6 transporters within a whole-organism context.

Grants

• The exocyst complex in dopamine transporter trafficking (2024)
  Source of Funding: FWF (Austrian Science Fund), Stand-alone project
  Coordinator of the collaborative project
• GAT-1 variants in epilepsy: molecular and rescue mechanisms (2022)
  Source of Funding: FWF (Austrian Science Fund), Stand-alone project
  Principal Investigator
• Pharmacological rescue of creatine transporter-1 variants (2018)
  Source of Funding: FWF (Austrian Science Fund), Stand-alone project
  Principal Investigator
• Pharmacochaperoning of the dopamine transporter (2014)
  Source of Funding: FWF (Austrian Science Fund), Stand-alone project
  Principal Investigator
• Evaluating lytic protein signatures as indicators of protective and pathological responses (2007)
  Source of Funding: EU, NoE
  Coordinator of the collaborative project
• Molecular structure-function relationship studies of the human noradrenaline transporter (2001)
  Source of Funding: Australian Federal Government, Department of Education and Training, Australian Postgraduate Award (APA: PhD Scholarship 2001-2005)
  Principal Investigator

Selected publications

1. Shah, N. et al. (2025) ‘Rescue of Epilepsy‐Associated Mutations of the Highly Conserved Glycine Residue 443 in the Human GABA Transporter 1’, The FASEB Journal, 39(11). Available at: https://doi.org/10.1096/fj.202403159rr.
2. Ün, D. et al. (2024) ‘Breaking the rules of SLC6 transporters: Export of the human creatine transporter‐1 from the endoplasmic reticulum is supported by its N‐terminus’, Journal of Neurochemistry, 168(9), pp. 2007–2021. Available at: https://doi.org/10.1111/jnc.16088.
3. Kasture, A.S. et al. (2023) ‘Drosophila melanogaster as a model for unraveling unique molecular features of epilepsy elicited by human GABA transporter 1 variants’, Frontiers in Neuroscience, 16. Available at: https://doi.org/10.3389/fnins.2022.1074427.
4. Bhat, S. et al. (2021) ‘Functional and Biochemical Consequences of Disease Variants in Neurotransmitter Transporters: A Special Emphasis on Folding and Trafficking Deficits’, Pharmacology & Therapeutics, 222, p. 107785. Available at: https://doi.org/10.1016/j.pharmthera.2020.107785.
5. El-Kasaby, A. et al. (2019) ‘Rescue by 4-phenylbutyrate of several misfolded creatine transporter-1 variants linked to the creatine transporter deficiency syndrome’, Neuropharmacology, 161, p. 107572. Available at: https://doi.org/10.1016/j.neuropharm.2019.03.015.