Milan Mrksich

About

Milan Mrksich is the Henry Wade Rogers Professor of Biomedical Engineering, Professor of Chemistry, and Professor of Cell and Developmental Biology at Northwestern University. His research group, the Laboratory for BioInterface Science and Engineering, focuses on the intersection of chemistry, biology, and engineering, with an emphasis on designing and synthesizing biologically active materials and applying these materials to relevant problems in biological and medical sciences. Much of his work involves the use of self-assembled monolayers of alkanethiolates on gold to create model surfaces that are structurally defined and capable of presenting ligands in spatially-organized patterns. He pioneered the development of 'dynamic substrates' that can switch ligand activities on and off in response to electrical or optical signals, facilitating studies on how adherent cells respond to changes in the extracellular matrix. His research has led to the discovery of novel ligands mediating cell adhesion and the development of robust surface chemistries for biochip arrays compatible with advanced analytical methods such as SAMDI mass spectrometry. His recent work includes creating defined systems to explore biochemical reactions and understand how enzyme and substrate localization control reaction networks.

Research topics

• Computer Science
• Biology
• Chemistry
• Organic chemistry
• Nanotechnology
• Materials science
• Paleontology
• Biochemical engineering
• Computational biology
• Biochemistry

Selected publications

• Computational planning of the synthesis of complex natural products

  Nature · 2020 · 271 citations

  , allowing it to 'strategize' over multiple synthetic steps. Using a Turing-like test administered to synthesis experts, we show that the routes designed by such a program are largely indistinguishable from those designed by humans. We also successfully validated three computer-designed syntheses of natural products in the laboratory. Taken together, these results indicate that expert-level automated synthetic planning is feasible, pending continued improvements to the reaction knowledge base an…

  DOI

• Bump-and-Hole Engineering Identifies Specific Substrates of Glycosyltransferases in Living Cells

  Molecular Cell · 2020 · 122 citations

  Studying posttranslational modifications classically relies on experimental strategies that oversimplify the complex biosynthetic machineries of living cells. Protein glycosylation contributes to essential biological processes, but correlating glycan structure, underlying protein, and disease-relevant biosynthetic regulation is currently elusive. Here, we engineer living cells to tag glycans with editable chemical functionalities while providing information on biosynthesis, physiological context…

  DOI

• Cell-free prototyping enables implementation of optimized reverse β-oxidation pathways in heterotrophic and autotrophic bacteria

  Nature Communications · 2022-06-01 · 78 citations

  articleOpen access

  Abstract Carbon-negative synthesis of biochemical products has the potential to mitigate global CO 2 emissions. An attractive route to do this is the reverse β-oxidation (r-BOX) pathway coupled to the Wood-Ljungdahl pathway. Here, we optimize and implement r-BOX for the synthesis of C4-C6 acids and alcohols. With a high-throughput in vitro prototyping workflow, we screen 762 unique pathway combinations using cell-free extracts tailored for r-BOX to identify enzyme sets for enhanced product selec…

  PublisherOA PDFDOI

• NADH inhibition of SIRT1 links energy state to transcription during time-restricted feeding

  Nature Metabolism · 2021-12-13 · 70 citations

  articleOpen access

  Abstract In mammals, circadian rhythms are entrained to the light cycle and drive daily oscillations in levels of NAD + , a cosubstrate of the class III histone deacetylase sirtuin 1 (SIRT1) that associates with clock transcription factors. Although NAD + also participates in redox reactions, the extent to which NAD(H) couples nutrient state with circadian transcriptional cycles remains unknown. Here we show that nocturnal animals subjected to time-restricted feeding of a calorie-restricted diet…

  PublisherOA PDFDOI

• High-throughput photocapture approach for reaction discovery

  Proceedings of the National Academy of Sciences · 2020 · 61 citations

  Modern organic reaction discovery and development relies on the rapid assessment of large arrays of hypothesis-driven experiments. The time-intensive nature of reaction analysis presents the greatest practical barrier for the execution of this iterative process that underpins the development of new bioactive agents. Toward addressing this critical bottleneck, we report herein a high-throughput analysis (HTA) method of reaction mixtures by photocapture on a 384-spot diazirine-terminated self-asse…

  PublisherOA PDFDOI

Recent grants

• Project 1: Design Rules for Spherical Nucleic Acids that Target Cancer

  NIH · $23.4M · 2021

• Collaborative Proposal: EMT/MISC Behavior Based Molecular Robotics

  NSF · $315k · 2008–2011

• NIH Grant R01GM063116

  NIH · $1.0M · 2006

Frequent coauthors

• George M. Whitesides

  36 shared

• Justin A. Modica

  Northwestern University

  33 shared

• Peter B. Dervan

  24 shared

• Jing Su

  Hainan University

  23 shared

• Richard P. Van Duyne

  22 shared

• Carolyn R. Bertozzi

  Stanford University

  22 shared

• Chad A. Mirkin

  Northwestern University

  21 shared

• Zachary A. Gurard‐Levin

  Charles River Laboratories (United States)

  18 shared

Labs

• Milan Mrksich GroupPI

Similar researchers at Northwestern University

• Shana Kelleyh-95
• Michael Marklh-88
• Igor Efimovh-83