California Institute of Technology

Mark William Budde

Michael B Elowitz

Lucy S Chong

Xiaojing Gao

Xiaofei Ge

Ronghui Zhu

Matthew Sun-min Kim

Long Cai

James Linton

Carlos Lois

Luis Sanchez Guardado

Yitong Ma

Michaelle N Mayalu

Amjad Askary

Disclosed herein include methods, compositions, and kits suitable for use in thresholding of protein signals. There are provided, in some embodiments, synthetic protein circuits that respond to inputs only above or below a certain threshold concentration. In some embodiments, the threshold value itself is tunable. Methods of treating a disease or disorder characterized by aberrant signaling are provided in some embodiments.

Synthetic system for tunable thresholding of protein signals

Disclosed herein include circuits, compositions, nucleic acids, populations, systems, and methods enabling cells to sense, control, and/or respond to their own population size. In some embodiments, an orthogonal communication channel allows specific communication between engineered cells. Also described herein, in some embodiments, is an evolutionarily robust 'paradoxical' regulatory circuit architecture in which orthogonal signals both stimulate and inhibit net cell growth at different signal concentrations. In some embodiments, engineered cells autonomously reach designed densities and/or activate therapeutic or safety programs at specific density thresholds. Methods of treatment are also provided in some embodiments.

Synthetic mammalian signaling circuits for robust cell population control

The present disclosure relates to systems, methods and compositions provided herein that include a compound protease. The compound protease can contain a protease domain, a cut site for another enzyme and an association domain. In some embodiments, the compound protease is part of a protein circuit.

Programmable protein circuits in living cells

Disclosed herein include systems, methods, compositions, and kits for in situ readout of barcodes, such as DNA barcodes. Barcode constructs containing a promoter (e.g., a phage promoter) that is inactive in live cells can be integrated in the genomes of cells. Cells can be fixed, and phage RNA polymerase can be used for transcription of the barcode to RNA transcripts. The RNA transcripts can be detected using, for example, fluorescent imaging and used to determine barcode sequences.

In situ readout of DNA barcodes

Some embodiments of the systems, methods and compositions provided herein relate to a compound protease. In some embodiments, the compound protease includes a protease domain and a cut site for another enzyme. In some embodiments, the compound protease includes an association domain. In some embodiments, the compound protease is part of a protein circuit.

Growing community of inventors

Arcadia, CA, United States of America

Mark William Budde