About Associate Professor Thomas Balle

Ion Channel Drug Discovery in an Academic Drug Delivery Setting. I am passionate about identification of new drug targets, lead molecules and development of new drugs for treatment of CNS disorders including dementia, neuropathic pain and schizophrenia. In my research group we have strong expertise in drug discovery including structure based drug design, molecular modelling, ion channel pharmacology and medicinal chemistry. We are part of a larger ion Channel Drug Discovery Unit and there is rich opportunity to participate multidisciplinary projects. I have a background in the pharmaceutical industry and we have strong links to both national and international pharmaceutical companies.

I am an expert in ion channel drug discovery and my aim is to use my expertise to identify new opportunities for development of drugs that can improve the lives of patients suffering from CNS disorders. I have a broad scientific profile with expertise in structure based drug design, molecular modelling, computational chemistry, medicinal chemistry and ion channel pharmacology. Together, these disciplines form the foundation for ion channel drug discovery. Keywords: Structure Based Drug Design, Molecular Modelling, Ion Channel Pharmacology, Electrophysiology, Computational Chemistry, Structural Biology, X-Ray Crystallography, Protein Expression & Purification.

Nicotinic Acetolcholine Receptors (nAChRs) play an improtant role in fast communication between cells. Dysfunctions or imbalances in nAChRs have been linked to a number of CNS disorders. In the past, many drug discovery efforts targeting nAChRs have failed, an important reason being lack of detailed understanding of how nAChRs work. In 2011 my group described the presence of a hitherto overseen agonist binding site on the receptor and acknowledging this site, we are now able to explain how different types of agonists, partial agonists and modulators work and hence also to rationally design new drug molecules with the desired effects. To facilitate drug discovery, we have pioneered the use of surrogate receptors in ion channel drug discovery. nAChRs are complicated receptors because they are assembled from several different subunits. With the surrogate receptors we have constructed simplified receptors where binding sites are engineered to be idetical or similar. These receptors produce simple responses that can be interpreted in a structural context.

Please contact me if you find the suggested projects interesting but do not find exactly what you are looking for. I am happy to discuss opportunities and tailor a project that matches your interests with our needs.

Selected publications

Harpsøe, K.; Ahring, P.K.; Christensen, J.K.; Jensen, M.L.; Peters, D.; Balle, T.: Unraveling the high and low sensitivity agonist responses of nicotinic acetylcholine receptors, J. Neuroscience, 2011, 31, 10759-10766

Shahsavar, A.; Ahring, P.K.; Olsen, J.A.; Krintel, C.; Kastrup, J.S. Balle, T.; Gajhede, M.: Acetylcholine-Binding Protein Engineered to Mimic the α4-α4 Binding Pocket in α4β2 Nicotinic Acetylcholine Receptors Reveals Interface Specific Interactions Important for Binding and Activity, Mol. Pharmacol., 2015, 88, 697-707

Bergmann, R.; Kongsbak, K.; Sørensen, P.L.; Sander, T.; Balle, T.: A Unified Model of the GABAA Receptor Comprising Agonist and Benzodiazepine Binding Sites, PloS ONE, 2013, 8(1): e52323. doi:10.1371/journal.pone.0052323

Rohde, L.Aa.H., Ahring, P.K.; Jensen, M.L.; Nielsen, E.Ø.; Peters, D.; Helgstrand, C.; Krintel, C.; Harpsøe, K.; Gajhede, M; Kastrup, J.S.; Balle, T.: Inter-subunit bridge formation governs agonist efficacy at nicotinic acetylcholine a4b2 receptors; Unique role of halogen bonding revealed, JBC, 2012, 287, 4248-4259

Shahsavar, A.; Kastrup, J.S.; Nielsen, E.Ø.; Kristensen, J.L.; Gajhede, M.; Balle, T.: Crystal Structure of Lymnaea Stagnalis AChBP Complexed with the Potent nAChR Antagonist DHβE Suggests a Unique Mode of Antagonism, PLoS ONE, 2012, 7(8), e40757, doi:10.1371/journal.pone.0040757

Krogsgaard-Larsen, N; Harpsøe, K; Kehler, J; Christoffersen, C.T.; Brøsen, P; Balle, T: Revision of the Classical Dopamine D2 Agonist Pharmacophore based on an Integrated Medicinal Chemistry, Homology Modelling and Computational Docking Approach, Neurochemical Research, 2014, 39, 1997-2007

Shahsavar, A.; Kastrup, J.S.; Gajhede, M.; Balle, T.; Structural Studies of Nicotinic Acetylcholine Receptors: Using Acetylcholine Binding Protein as a Structural Surrogate, Basic Clin. Pharmacol., 2016, Doi: 10.1111/bcp t.12528

Ahring, P.K.; Olsen, J.A.; Nielsen, E.Ø.; Peters, D.; Pedersen, M.H.F.; Rohde, L.A.H.; Kastrup, J.S.;  Shahsavar, A.; Indurthi, D.C.; Chebib, M.; Gajhede, M.; Balle, T.: Engineered α4β2 Nicotinic Acetylcholine Receptors as Models for Measuring Agonist Binding and Effect at the Orthosteric Low-affinity α4-α4 Interface, Neuropharmacology, 2015, 92, 135-145

Olsen, J.A.; Ahring, P.K.; Kastrup, J.S.: Gajhede, M.; Balle, T.: Structural and Functional Studies of the Modulator NS9283 Reveal Agonist-Like Mechanism of Action at α4β2 Nicotinic Acetylcholine Receptors, JBC, 2014, 289, 24911-24921