Tapahtumakalenteri
Dissertation: Hasan Ugurlu
Opponent: Professor Olivier Schwartz, Institut Pasteur
Dissertation: Rishi Banerjee
Opponent: Professor Luis Lopez, University of Granada
HiLIFE / Biomedicum Helsinki seminar by Thomas Mrsic-Flogel: Decision Making: From Brain-Wide Dynamics to Multi-regional Circuit Mechanisms
Dear All,
Professor Thomas Mrsic-Flogel from the Sainsbury Welcome Center, UCL, UK will give a talk in the HiLIFE seminar series:
Decision Making: From Brain-Wide Dynamics to Multi-regional Circuit Mechanisms
Tom Mrsic-Flogel is Director of the Sainsbury Wellcome Centre for Neural Circuits and Behaviour (SWC), and Professor of Neuroscience at University College London. He was previously Associate Professor of Neuroscience at the Biozentrum, University of Basel. His lab has contributed to three interrelated areas of neuroscience: identifying neural circuit principles of cortical computations; how learning shapes these circuits to improve sensory processing; and how multi-regional circuits contribute to cognition and sensory-guided behaviours. As Director of the SWC, his vision is to develop a unique institute in which experimental and theoretical neuroscientists join forces to generate major conceptual breakthroughs in the understanding of how brain function gives rise to intelligent behaviour. He is committed to finding new, collaborative approaches to scientific research and novel ways to drive progress in research culture.Welcome to this exciting seminar!
Abstract: Throughout our lives we make countless decisions based on learned associations between sensory inputs and beneficial actions. However, flexible behaviour requires that these learned associations only influence our actions when they serve our current goals. While frontal cortex is known to be critical for this behavioural flexibility by representing internal goals and context-dependent rules, and the basal ganglia are essential for implementing learned sensorimotor associations, the mechanisms by which frontal regions exert control over these action selection circuits remain poorly understood. Using brain-wide recordings in mice, we demonstrate that learning establishes distributed sensorimotor transformations, enabling sustained representations of relevant sensory information in premotor regions of frontal-motor cortex, thalamus, basal ganglia, midbrain and cerebellum. Neural dynamics in these regions couple sensory evidence to movement preparation while remaining distinct from movement execution. At the circuit level, targeted activity manipulations and recordings reveal that the anterior tip of secondary motor cortex (atMOs) implements “cognitive control” through an activity 'state clamping' mechanism, dynamically controlling population dynamics in the striatum to enable goal-directed sensorimotor mapping. This mechanism operates in a neural dimension orthogonal to evidence accumulation, allowing precise control over whether sensory evidence leads to action. Together, these findings reveal how brain-wide dynamics coordinate with multi-regional circuit mechanisms to selectively engage learned sensorimotor transformations according to current behavioural goals.
Welcome to this exciting seminar!
Eero Castrén
Tom is available for meeting with local scientists. If you are interested in talking to him, please contact Eero.
Selected publications:
Brain-wide dynamics linking sensation to action during decision-making. Khilkevich A, ... & Mrsic-Flogel TD. Nature 2024 https://doi.org/10.1038/s41586-024-07908-w
Cooperative thalamocortical circuit mechanism for sensory prediction errors. Furutachi S. ... Mrsic-Flogel, TD, Hofer S. Nature 2024 https://doi.org/10.1038/s41586-024-07851-w
Cortical feedback loops bind distributed representations of working memory. Voitov I, Mrsic-Flogel TD. Nature 2022 (doi: 10.1038/s41586-022-05014-3)
iCAN science seminar on Overcoming Undruggable Nature of Most Common Human Oncogene, K-Ras with Prof. Kevan Shokat
Hosts: Olli Silvennoinen, Ville Paavilainen, Rafa Najumudeen
If you wish to meet with Prof. Shokat during his visit, please contact Rafa
Najumudeen (arafath.najumudeen@helsinki.fi).
Abstract: Somatic
mutations in the small GTPase K-Ras are the most common activating lesions
found in human cancer and are generally associated with poor response to
standard therapies. Efforts to directly target this oncogene have faced
difficulties due to its picomolar affinity for GTP/GDP and the absence of known
allosteric regulatory sites. In the seminar, prof. Shokat will discuss the
development of small molecules that irreversibly bind to a common oncogenic
mutant, K-Ras G12C. These compounds rely on the mutant cysteine for binding and
therefore do not affect the wild type protein (WT). Prof. Shokat will
also discuss ways to leverage immune cell killing of K-Ras G12C cells treated
by combining small molecule inhibitors and bi-specific T-Cell engagers.
Prof. Shokat is a great speaker and his talk will be of
relevance and interest for translational biomedicine, chemical
biology, protein biochemistry and clinical medicine.
***
Professor Shokat is a pioneer of modern chemical biology, using innovative approaches to develop powerful molecular tools to advance basic knowledge and combat devastating diseases. Shokat´s research has shifted the paradigm of targeted cancer therapy by drugging an “undruggable” protein and paving the way for future advances. In 2013 Shokat described the concept of targeting the most common human oncogene K-Ras. The 1st Ras drug sotorasib was approved in 2021 for non-small cell lung cancer, and presently they are developing drugs for KRAS mutations common in colorectal and pancreatic cancer. In addition, to small GTPases, Prof. Shokat has contributed to chemical tools and new drugs targeting protein kinases using a combination of protein engineering and organic chemical synthesis. His discoveries have thus far been commercialized by approximately 10 companies.
Prof. Shokat is a member of National Academy of Sciences, National Academy of Medicine, American Academy of Arts and Sciences, and recipient of numerous awards, e.g. Sjöberg Prize in 2023.
iCAN science seminar on Metabolic Challenges and Therapeutic Opportunities in Pancreatic Cancer with Assoc. Prof. Nada Kalaany
Host: Dr. Anna Vähärautio
If you wish to
meet with Dr. Kalaany during her visit, please contact Anna
Vähärautio (anna.vaharautio@helsinki.fi).
***
Nada Kalaany received her PhD from UT Southwestern Medical Center (at Dallas, Texas), where she studied the role of nuclear hormone receptors in lipid metabolism. She completed her post-doctoral training in Cancer Metabolism at the Whitehead Institute at MIT where she identified a mechanism regulating the sensitivity of tumors to diet restriction. She is currently Associate Professor at Harvard Medical School, Boston Children’s Hospital where her lab focuses on identifying in vivo metabolic dependencies in cancers and understanding the metabolic crosstalk between tumors and their hosts.