Dr. Timurs Maculins
Timurs was born in Riga, Latvia, where he studied medicine in Riga Stradiņš Medical University. He has joint academic research via a Master of Science degree at the Erasmus Medical Centre Rotterdam with the support of the Huygens Scholarship awarded by the Netherlands Organization for International Cooperation in Higher Education. Timurs pursued his interests in fundamental research by joining the laboratory of Karim Labib at the Manchester Cancer Research Centre in the United Kingdom after receiving a doctoral studentship from Cancer Research UK. Using the budding yeast as a model organism in his doctoral work, Timurs studied a role of a novel enzyme, known as SCFDia2 ubiquitin ligase, during DNA replication in the S phase of the cell cycle. Tim’s most significant discovery is an observation that cells lacking SCFDia2 accumulate ‘un-disassembled’ replication complexes at the end of S phase, which is rescued by re-expression of the ligase. This constitutes a key step of a fundamental mechanism, known as replisome disassembly, which Timurs and his colleagues co-discovered in eukaryotes.
Timurs continued his career as a postdoctoral scientist in the pharmaceutical industry in a collaborative project between the AstraZeneca High-Throughput Screening Centre and the academic laboratory headed by Ronald Hay. Following his interests in ubiquitin drug discovery, Timurs developed a novel approach for modulating the activity of mammalian ubiquitin ligases with chemical compounds. This field of drug discovery holds a great therapeutic potential, but in the absence of reliable screening technologies remains largely unexplored. Working in close collaboration with Hay’s laboratory, Timurs has developed a robust method for pharmacological inhibition of ubiquitin ligases in mammalian cells and utilized it to discover small molecule inhibitors against Rnf8 enzyme that regulates DNA damage response.
In late 2015 Timurs joined a collaborative project between the laboratory headed by Ivan Dikic and Fraunhofer IME for developing innovative approaches for pharmacological targeting of the ubiquitin system. Most recently, Timurs has received the Human Frontier Science Program postdoctoral fellowship, which he will utilize for studying the role played by ubiquitin ligase-like effectors during infection by lethal bacterial pathogens.
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