Our co-Leader, Suvam, had a chance to meet Prof. Ranabir Das, and Anindita Puri, NCBS, who provided their inputs on PROTAC. They gave us insights on types of ligands and protein purification processes.
With the progress of time, we came across the concept of phosphomimetics. To understand this concept better, we consulted Surabhi Chandra, PhD, Prof. Hussain’s lab, and Shrivallabh Deshpande, PhD, Prof. Nair’s lab, who suggested that we give it a shot.
To seek expert opinion, we approached Prof. Muddashetty, who redirected us to Prof. Sivaprakasam Ramamoorthy.Prof. Ramamoorthy was not convinced of whether phosphomimetics would work for our system and suggested that we try it or consult a biochemist. He also provided many insights about tauopathies, and about the industries related to them. He also put forward the question of competing with large scale biotech giants and suggested that we should reform our research in order to make it marketable. He keenly listened our plan of action and participated in improving it. That short meeting changed many non-research aspects of our work.
To learn more about phosphomimetics, we approached Prof. Saravanan Palani, Biochemistry, IISc. He suggested that we try phosphomimetics, by switching out threonine or serine with aspartic acid or glutamic acid, in different combinations. He suggested that we check the phosphomimetic tau using molecular simulation and compare it with tau phosphorylated in the human body. He gave us insights into phosphomimetics and how we could test the similarity of a phosphomimetic and phosphorylated protein using spectroscopic techniques.
For further information, we approached to Paulomi Sanyal, PhD, Prof. Ashok Sekhar’s lab, Molecular Biophysics Unit, IISc, who works on phosphomimetics and the changes involved. She gave us first-hand information about how she employs it in her work and how we could incorporate it in ours. She also helped us design the phosphomimetic plasmid.