David Holcman Explained

David Holcman is an applied mathematician, biophysicist and computational biologist at École Normale Supérieure in Paris. He is known for his work on the narrow escape problem, based on analysis of the Laplace equation,^{[1] [2]} the redundancy principle in biology based on extreme statistics,^{[3] [4] [5]} the modeling of molecular trafficking in neurobiology, of diffusion and electrodiffusion in nanodomains such as dendritic spines, the modeling of neuronal networks dynamics such as Up and Down states in electrophysiology. He developed multiscale methods and simulations to analyse large amount of molecular super-resolution trajectories, and polymer physics modeling and analysis to study cell nucleus organization.^[6] These computational approaches led to several verified predictions in the life sciences such as nanocolumn organization of synapses^{[7] [8]} or astrocytic protrusion penetrating neuronal synapses,^[9] molecular ER organization in dendritic spines and many more. The narrow escape theory was recently verified in physical experiments.^[10]

Works

His research interests include mathematical biology, stochastic processes, data modeling, computational methods, stochastic simulations, theory of cellular microworld, neuronal networks, computational biology and neuroscience, asymptotic approaches in partial differential equations, predictive medicine, electroencephalography (EEG) analysis, and modeling organelles in cells.^[11] Other contributions concern methods of analyzing single particle trajectories, calcium dynamics in dendritic spines and the development of statistical methods, polymer models, analysis and simulations to study chromatin and nucleus organization. His recent works concern predicting the brain state transition during general anesthesia based on real-time operative multi-dimensional dynamics including time-frequency patterns and signal suppressions.

Publications

Holcman has more than 220 published journal articles and has registered 2 patents.

He is the co-author of the books:

• David Holcman and Zeev Schuss, Stochastic Narrow Escape in Molecular and Cellular Biology: Analysis and Applications, 2015-09-08,
• David Holcman (editor), Stochastic Processes, Multiscale Modeling, and Numerical Methods for Computational Cellular Biology, 2017-10-04,
• David Holcman and Zeev Schuss, Asymptotics of Elliptic and Parabolic PDEs: and their Applications in Statistical Physics, Computational Neuroscience, and Biophysics, 2018-05-25

Press coverage

• To celebrate the first winners of the Europeran Research council (ERC) in 2007, an international meeting was organized in Paris, so that they could discuss their vision and research plan for the future.
• The narrow escape theory has inspired the Fargo TV series in 2017.
• The novel nanoscale molecular organization underlying calcium dynamics in synapses, revealed by combining multidisciplinary approaches (live cell imaging, modeling, simulation, super-resolution) and published in 2021 brought novel concepts to the basis of memory and memory architecture.
• During the year 2019-2022, the work on Electro-encephalogram (EEG) analysis led to several applications to better monitor and control anesthesia doses, popularized in "Pour La science".
• The work on computing the time for spermatozoa to reach an egg in the uterus received the Pineapple Science Award (Math Prize), the Chinese equivalent of the Ig Noble Prize in 2018.
• The notion of time for living organism can be defined as the first time the shortest telomere reaches a minimal threshold value: it is a random variable, controlled by the extreme statistics associated to telomere dynamics. "How cells are counting time?": this work was popularized in the viewpoint article in 2013: The Life and Death of Cells.
• The discovery reported in 2014, that astrocytes could invade the synaptic cleft under some specific conditions was recognized as a key result for controling synaptic function "Invasion of Astrocytes: modeling driving experiments"
• In 2011, mathematical modeling was at a turning point as it was becoming predictive for molecular and cellular: this moment was summarized in an interview with the CNRS journal: "When biology becomes mathematics...".
• In 2022, the adaptative algorithm to predict the sensitivity to general anesthesesia developed by the Holcman's group gained interest from the national french newspaper "Le Monde": Une équipe française développe des algorithmes d’analyse en temps réel des données de l’EEG, pendant que le patient est sédaté.

Awards

Holcman has received several awards, including a Sloan-Keck fellowship award (2002) a Marie-Curie Award^[12] (2013), and a Simons Fellowship. He is also recipient of 2 ERCs: an ERC Starting Grant^[13] in mathematics (2007) and an ERC-Advanced Grant in computational biology^[14] (2019).

Notes and References

1. Mangeat . M . Rieger . H . 2019-10-18 . The narrow escape problem in a circular domain with radial piecewise constant diffusivity . Journal of Physics A: Mathematical and Theoretical . 52 . 42 . 424002 . 10.1088/1751-8121/ab4348 . 1906.06975 . 2019JPhA...52P4002M . 189928197 . 1751-8113.
2. Schuss . Z. . 2012-10-01 . The Narrow Escape Problem—A Short Review of Recent Results . Journal of Scientific Computing . en . 53 . 1 . 194–210 . 10.1007/s10915-012-9590-y . 254702232 . 1573-7691.
3. Redner . S. . Meerson . B. . 2019-03-01 . Redundancy, extreme statistics and geometrical optics of Brownian motion: Comment on "Redundancy principle and the role of extreme statistics in molecular and cellular biology" by Z. Schuss et al. . Physics of Life Reviews . en . 28 . 80–82 . 10.1016/j.plrev.2019.01.020 . 30718199 . 2019PhLRv..28...80R . 73448264 . 1571-0645.
4. Sokolov . Igor M. . 2019-03-01 . Extreme fluctuation dominance in biology: On the usefulness of wastefulness: Comment on "Redundancy principle and the role of extreme statistics in molecular and cellular biology" by Z. Schuss, K. Basnayake and D. Holcman . Physics of Life Reviews . en . 28 . 88–91 . 10.1016/j.plrev.2019.03.003 . 30904271 . 2019PhLRv..28...88S . 85496733 . 1571-0645.
5. Coombs . Daniel . 2019-03-01 . First among equals: Comment on "Redundancy principle and the role of extreme statistics in molecular and cellular biology" by Z. Schuss, K. Basnayake and D. Holcman . Physics of Life Reviews . en . 28 . 92–93 . 10.1016/j.plrev.2019.03.002 . 30905554 . 2019PhLRv..28...92C . 85497459 . 1571-0645.
6. Blythe . Richard A. . MacPhee . Cait E. . 2013-11-27 . The Life and Death of Cells . Physics . en . 6 . 22 . 129 . 10.1103/PhysRevLett.111.228104. 24329474 .
7. Guzikowski . Natalie J. . Kavalali . Ege T. . 2021 . Nano-Organization at the Synapse: Segregation of Distinct Forms of Neurotransmission . Frontiers in Synaptic Neuroscience . 13 . 796498 . 10.3389/fnsyn.2021.796498 . 35002671 . 8727373 . 1663-3563. free .
8. Tang . Ai-Hui . Chen . Haiwen . Li . Tuo P. . Metzbower . Sarah R. . MacGillavry . Harold D. . Blanpied . Thomas A. . August 2016 . A trans-synaptic nanocolumn aligns neurotransmitter release to receptors . Nature . en . 536 . 7615 . 210–214 . 10.1038/nature19058 . 27462810 . 5002394 . 2016Natur.536..210T . 1476-4687.
9. Welberg . Leonie . April 2014 . Invasion of the astrocytes! . Nature Reviews Neuroscience . en . 15 . 4 . 207 . 10.1038/nrn3720 . 24619346 . 13189654 . 1471-0048.
10. Meiser . Elisabeth . Mohammadi . Reza . Vogel . Nicolas . Holcman . David . Fenz . Susanne F. . 2023-11-17 . Experiments in micro-patterned model membranes support the narrow escape theory . Communications Physics . en . 6 . 1 . 1–10 . 10.1038/s42005-023-01443-2 . 2399-3650.
11. Web site: David Holcman . 2023-09-14 . scholar.google.com.
12. Web site: Home Marie Skłodowska-Curie Actions . 2023-03-22 . marie-sklodowska-curie-actions.ec.europa.eu.
13. Web site: David Holcman INSB . 2023-03-22 . www.insb.cnrs.fr . 31 July 2007 . fr.
14. Web site: David Holcman, lauréat ERC Advanced Grants ENS . www.ens.psl.eu . 2023-03-22.