Associate Professor of Bioengineering
Core Faculty Molecular Engineering and Science Institute
Institute for Stem Cell and Regenerative Medicine
UW Center of Excellence for the Neurobiology of Addiction, Pain and Emotion
berndtuw@uw.edu
South Lake Union campus, 850 Republican St., Brotman Building

Andre Berndt

Lab Website

How I am inventing the future of medicine

My lab develops a wide array of biosensors, including fluorescent calcium, reactive oxygen species, cAMP, and voltage indicators, as well as glutamate, GABA, opioid, and dopamine sensors. Validating and engineering these tools showed me the limitations of current technology and motivated me to incorporate faster, high-throughput, and machine-learning approaches for future tool development. My vision is to overcome the current slow engineering cycles for biosensors. Specifically, I aim to rapidly develop spectrally diverse biosensors for neuromodulators, which could visualize brain signaling with unprecedented accuracy and specificity. My lab has developed an innovative high-throughput engineering pipeline and improved fluorescent dopamine and opioid sensors by screening large mutational variant libraries. We also developed an innovative, data-driven approach to protein engineering by using machine learning to engineer record-setting fluorescent calcium indicators. Furthermore, we used structure-guided design, and AI-predicted protein structure to engineer fluorescent sensors for reactive oxygen species. These include far-red shifted sensors with improved pH and photostability.

Protein Engineering
High-Throughput Assays
Machine Learning
Neuroscience
Optogenetics

We are a molecular design lab which develops fluorescent biosensors for detecting biochemical signals in neuronal networks in real time. Our goal is to monitor the activity of neurotransmitter, neuromodulators, hormones, ions and intracellular signaling molecules in live tissue and behaving animals at high spatial and temporal resolution.  These sensors provide accurate, multidimensional information about information processing in neurons and neuronal networks. We aim to use these tools to identify impaired network dynamics in animal models for neurological disorders which will close critical knowledge gaps in our understanding of diseases such as autism and epilepsy.  One big advantage is that these sensors are genetically encoded proteins which means they can be expressed in virtually any cell type by using virus or plasmid DNA. Thus, they are universally applicable and we seek to expand applications into other cell types such as cardiac, pancreatic and stem cells.

PhD in Biophysics, 07/2011, Humboldt University Berlin, Germany
Postdoctoral Fellow, 2011-2017, Training in Optogenetics/Neuroscience, Stanford University

I used structure-guided protein engineering to develop new variants of the light-gated ion channel channelrhodopsin. For example, I designed the first channelrhodopsins with fast and slow kinetics for precise stimulation of neuronal signals, lasting from a few milliseconds to minutes and hours. Furthermore, I developed several chloride-selective channelrhodopsins that replicate a physiologically relevant mechanism to inhibit neuronal activity by shunting and allow for the remote control of neuronal chloride homeostasis. These tools and their successors are now essential components in the field of optogenetics. I used these approaches in various applications, which range from in vitro studies to behavioral tests in rodents. I believe that a fundamental understanding of the molecular basis of genetically encoded tools and a profound understanding of cell physiology is crucial for advancing optogenetic techniques

2024 Excellence in Research Award from the UW Department of Bioengineering
2023 Excellence in Research Award from the UW Department of Bioengineering
2023 McKnight Technology in Neuroscience Award
2020 NARSAD Young Investigator Grant, Brain and Behavior Research Foundation
2019 New Frontiers in Research Fund, Canadian Institutes of Health Research
2018 Finalist Beckman Young Investigator, Arnold and Mabel Beckman Foundation
2018 Fay/Frank Seed Grant, Brain Research Foundation
2017 Selected for Next Generation Leader Council, Allen Institute for Brain Science
2011 Postdoctoral fellowship, German Academic Exchange Service
2011 Best Ph.D. thesis, Humboldt University Berlin
2010 Pre-doctoral fellowship, European Molecular Biology Organization
2007 2010 Pre-doctoral fellowship, Leibniz Graduate School for Molecular Biophysics

BioEng 317 Biomedical Signals And Sensors Laboratory
BioEng 463/563 Optogenetics

Michael Rappleye, Sarah J. Wait, Justin Daho Lee, Jamison C. Siebart, Lily Torp, Netta Smith, Jeanot Muster, Kenneth A. Matreyek, Douglas M. Fowler, and Andre Berndt. Optogenetic Microwell Array Screening System: A High-Throughput Engineering Platform for Genetically Encoded Fluorescent Indicators. ACS Sensors, 2023 Nov 24;8(11):4233-4244. doi: 10.1021/acssensors.3c01573. Epub 2023 Nov 13.

Sarah J. Wait, Marc Expòsit, Sophia Lin, Michael Rappleye, Justin Daho Lee, Samuel A. Colby, Lily Torp, Anthony Asencio, Annette Smith, Michael Regnier, Farid Moussavi-Harami, David Baker, Christina K. Kim & Andre Berndt., Machine Learning Ensemble Directed Engineering of Genetically Encoded Fluorescent Calcium Indicators. Nature Computational Science, 2024 Mar;4(3):224-236. doi: 10.1038/s43588-024-00611-w. Epub 2024 Mar 21. PMID: 38532137.

Justin Daho Lee, Amanda Nguyen, Zheyu Ruby Jin, Aida Moghadasi, Chelsea E. Gibbs, Sarah J. Wait, Kira M. Evitts, Anthony Asencio, Samantha B Bremner, Shani Zuniga, Vedant Chavan, Andy Williams, Netta Smith, Michael Regnier, Jessica E. Young, David Mack, Elizabeth Nance, Patrick M. Boyle, Andre Berndt. Far-red and sensitive sensor for monitoring real-time H2O2 dynamics with subcellular resolution and in multi-parametric imaging applications. bioRxiv, 2024, doi: doi.org/10.1101/2024.02.06.579232

Justin Daho Lee, Woojin Won, Kandace Kimball, Yihan Wang, Fred Yeboah, Kira M. Evitts, Carlie Neiswanger, Selena Schattauer, Michael Rappleye, Samantha B Bremner, Changho Chun, Netta Smith, David L. Mack, Jessica E. Young, C. Justin Lee, Charles Chavkin, Andre Berndt, Structure-guided engineering of a fast genetically encoded sensor for real-time H2O2 monitoring. bioRxiv, 2024, doi: doi.org/10.1101/2024.01.31.578117

Klima JC, Doyle LA, Lee JD*, Rappleye M, Gagnon LA, Lee MY, Barros EP, Vorobieva AA, Dou J, Bremner S, Quon JS, Chow CM, Carter L, Mack DL, Amaro RE, Vaughan JC, Berndt A, Stoddard BL, Baker D: Incorporation of sensing modalities into de novo designed fluorescence-activating proteins. Nature Communications, 2021 Feb 8;12(1):856. doi: 10.1038/s41467-020-18911-w.

Kato HE, Kim YS, Paggi JM, Evans KE, Allen WE, Richardson C, Inoue K, Ito S, Ramakrishnan C, Fenno LE, Yamashita K, Hilger D, Lee SY, Berndt A, Shen K, Kandori H, Dror RO, Kobilka BK, Deisseroth K. Structural mechanisms of selectivity and gating in anion channelrhodopsins. Nature (2018). PubMed PMID: 30158697; PubMed Central PMCID: PMC6317992.

Berndt A, Lee SY, Wietek J, Ramakrishnan C, Steinberg EE, Rashid AJ, Kim H, Park S, Santoro A, Frankland PW, Iyer SM, Pak S, Ährlund-Richter S, Delp SL, Malenka RC, Josselyn SA, Carlén M, Hegemann P, Deisseroth K. Structural foundations of optogenetics: Determinants of channelrhodopsin ion selectivity. Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):822-9. PubMed PMID: 26699459; PubMed Central PMCID: PMC4743797.

Rajasethupathy P, Sankaran S, Marshel JH, Kim CK, Ferenczi E, Lee SY, Berndt A, Ramakrishnan C, Jaffe A, Lo M, Liston C, Deisseroth K. Projections from neocortex mediate top-down control of memory retrieval. Nature. 2015 Oct 29;526(7575):653-9. PubMed PMID: 26436451; PubMed Central PMCID: PMC4825678.

Tee BC, Chortos A, Berndt A, Nguyen AK, Tom A, McGuire A, Lin ZC, Tien K, Bae WG, Wang H, Mei P, Chou HH, Cui B, Deisseroth K, Ng TN, Bao Z. A skin-inspired organic digital mechanoreceptor. Science. 2015 Oct 16;350(6258):313-6. PubMed PMID: 26472906.

Berndt A, Lee SY, Ramakrishnan C, Deisseroth K. Structure-guided transformation of channelrhodopsin into a light-activated chloride channel. Science. 2014 Apr 25;344(6182):420-4. PubMed PMID: 24763591; PubMed Central PMCID: PMC4096039.

Gunaydin LA, Yizhar O, Berndt A, Sohal VS, Deisseroth K, Hegemann P. Ultrafast optogenetic control. Nature Neuroscience. 2010 Mar;13(3):387-92. PubMed PMID: 20081849.

Berndt A, Yizhar O, Gunaydin LA, Hegemann P, Deisseroth K. Bi-stable neural state switches. Nature Neuroscience. 2009 Feb;12(2):229-34. PubMed PMID: 19079251.

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