Axial - Berkeley #1

Analysis of exciting Berkeley life sciences inventors and their inventions

Inventors have always had the opportunity to create unique business models. Going to school in Berkeley and living a few blocks from campus, there is a storehouse of talented inventors in Berkeley. The ultimate goal is to form companies that otherwise wouldn’t have gotten started for a variety of reasons, access to capital, perspective, and belief with the purpose to create unique business models and make inventions more accessible. The core thesis is to use inventions to create unique business models for founder-driven life sciences companies; ultimately, it’s easier to do business with a founder. It would be great for important and large businesses to be walking distance within Berkeley. 

In short, Berkeley is an incredible source of scientific creativity and business potential. Being relatively ignored but connected to a center of capital, Berkeley has the opportunity to create the world’s next important companies.

Xu Lab

Focused on physiochemical tools to functionally observe cells and molecules at a super-resolution.

Recent

• Published a really interesting paper - https://www.biorxiv.org/content/biorxiv/early/2019/02/25/559484.full.pdf- inventing single-molecule displacement/diffusivity mapping (SMdM) to map intracellular dynamics discovering positive but not negative charge of the diffuser impedes diffusion.

• Gave a talk at Stanford. - https://chemistry.stanford.edu/events/physical-chemistry-seminar-professor-ke-xu-uc-berkeley

Past

• In Nature Methods - https://www.nature.com/articles/nmeth.3528combined spectroscopy and super-resolution microscopy to image cells with 4 dyes. A very useful invention to map out complex cellular events. Next steps are toward live cells and new fluorophores. 

Kuriyan Lab

Structural studies of cellular signal transduction.

Recent

• Studying Ras activation (important for IO) through SOS activation - http://science.sciencemag.org/content/363/6431/1098- through single-molecule microscopy, they discovered SOS's activating molecules first must make a phase transition and condense.

Past

• Deep mutational analysis of EGFR autophosphorylation sites- https://www.ncbi.nlm.nih.gov/pubmed/30012625- discovered phosphosites in EGFR make the trade-off reducing the ability to recruit complement effector proteins after phosphorylation in order to reduce off-pathway activation.

M. Chang Lab

Studying complex metabolic networks for sustainable chemical synthesis.

Recent

• Discovery of a pathway for terminal-alkyne amino acid biosynthesis - https://www.nature.com/articles/s41586-019-1020-y- by discovering a unique pathway in S. cattleyaproducing an amino acid with a terminal alkyne, create a new technology for click chemistry and a discovery process to identify new non-standard amino acids for bioorthogonal reactions.

Past

• Engineering fluorine metabolism coupled with fluoropolymer production in living cells - https://onlinelibrary.wiley.com/doi/epdf/10.1002/anie.201706696- fluorine is rarely found in natural metabolism; as a result, a chassis focused on organofluorine metabolism was created with applications in generating fluorinated natural products for drugs and chemicals.

C. Chang Lab

Using bioinorganic chemistry to study the role of metals in health and energy.

Recent

• Invented a platform for tissue-specific metal ion delivery - https://pubs.acs.org/doi/abs/10.1021/jacs.8b08014?journalCode=jacsat- demonstrated the use of the platform through copper supplementation to the liver.

Past

• Discovered copper regulates lipolysis - https://www.nature.com/articles/nchembio.2098

Conboy Lab

Using biological engineering to repair, regenerate, and maintain tissues as we age.

Recent

• Recently published a chapter in Springer - https://www.ncbi.nlm.nih.gov/pubmed/30779008- arguing that MAP kinase (MAPK) declining with age perturbs tissue homeostasis and repair by dedicated stem cells through the Notch and Jak/STAT pathways.

Past

• In Nature Communications - https://www.ncbi.nlm.nih.gov/pubmed/28935952- invented a method to selectively label proteins in vivoto detect changes in tissue regeneration and parabiosis.

Murthy Lab

Developing new tools for molecular imaging and drug delivery.

Recent

• Invented a fluorescent surfactant (i.e. FEDEX) to increase the ability of lipofectamine to deliver Cas9 RNPs through endosomal disruption and enable the ability to sort gene edited cells by flow cytometry. https://pubs.rsc.org/en/Content/ArticleLanding/2019/CC/C9CC00261H#!divAbstract

• Worked on implementing an indirect-ELISA to differentially detect E. coli and P. aeruginosa. https://www.sciencedirect.com/science/article/pii/S0167701218309758

Past

• Invented nanoparticles to deliver CRISPR to the brain to rescue mice with fragile X syndrome - https://www.nature.com/articles/s41551-018-0252-8- invention formed the basis of GenEdit.

Savage Lab

Engineering proteins to understand fundamental biochemical processes.

Recent

• By inventing CRISPR-Cas9 circular permutants, created a scaffold to add fusions and domains activated for external signals - https://www.sciencedirect.com/science/article/pii/S0092867418315836- used the tools to invent a protease-sensing Cas9 (ProCas9) embuing programmability to the gene editing effector. For example, ProCas9 has use cases to improve gene editing safety and selectivity.

Past

• Conducted a systematic screen to find genes related to CO2 concentrating mechanisms (CCMs) - https://www.biorxiv.org/content/10.1101/476713v2- the work discovered two genes related to inorganic carbon transport.

Drubin/Barnes Lab

Studying actin-mediated membrane trafficking.

Recent

• For clathrin-mediated endocytosis (CME), showed type I myosin is essential to anchor the actin assembly machinery to the plasma membrane- http://jcb.rupress.org/content/218/4/1138- with the assay set up, the next steps are to assess the role of type I myosin in other trafficking events.

• Using lattice light-sheet microscopy, recorded clathrin-mediated endocytosis (CME) in about 35 cells per run - https://www.ncbi.nlm.nih.gov/pubmed/30188768 - this work is a tour de force, laying the basis to understand endocytosis at an unprecedented scale. With new drug modalities coming online over the next decade, our understanding of endocytosis is still very limited. However, work like this can improve our ability to engineer therapeutics that can more easily get into cells and specific compartments.

Past

• Invented an in vitroassay to measure the growth of single microtubules in reconstituted budding yeast lysates. http://jcs.biologists.org/content/early/2018/08/31/jcs.219386

Portnoy Lab

Studying fundamental processes of intracellular pathogens.

Recent

• Discovered a unique flavin-based extracellular electron transfer (EET) mechanism in Listeria monocytogenes. https://www.ncbi.nlm.nih.gov/pubmed/30209391

Past

• By genetic analysis, discovered that Listeria monocytogenes can escape xenophagy (i.e. a way to trap and delivery microbes to degradative compartments) through PlcA/B and ActA. https://www.ncbi.nlm.nih.gov/pubmed/29279409

Hammond Lab

Engineering nucleic acids for molecular imaging and gene control and studying the role cyclic dinucleotides in cell signaling.

Recent

• Invented the first chemiluminescent biosensors for cyclic di-GMP- https://pubs.acs.org/doi/10.1021/acschembio.7b01019- bacterial colonization is partly controlled by cyclic di-GMP, an intracellular signal involved in motility and biofilm formation.

Past

• Invented a method to quantify structured RNA - https://rnajournal.cshlp.org/content/20/7/1153- importance is centered around thermal hydrolysis allowing precise measurement of RNAs at neutral pH negating the need for calibration curves, reaction quenching, and expensive reagents.

• Invented a fluorescent biosensor for 2′,3′-cGAMP - https://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(16)30392-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2451945616303920%3Fshowall%3Dtrue- with important use to measure cGAS activity and inhibition in a high-throughput manner.

Anderson Lab

Developing new tools and applications for organism design.

Past

• Designed synthetic auxotrophs dependent on the ligand, benzothiazole to create a biosafety-capable chassis - https://pubs.acs.org/doi/abs/10.1021/acssynbio.5b00085- forming the basis of Synvivia. 

• In a really neat paper, used DNA-linked enzyme-coupled assay (DLEnCA) to profile an enzyme’s substrate specificity and their kinetics - https://pubs.acs.org/doi/10.1021/acschembio.6b00652- the key breakthrough, is the use of next-generation sequencing (NGS) to rapidly decode enzyme function.

Cate Lab

Engineering and studying translation for health, industrial applications, and energy.

Recent

• Conducted a CRISPRi screen to identify genetic modulator of translation - https://www.ncbi.nlm.nih.gov/pubmed/30875366 - identified the ubiquitin binding protein ASCC2 and the helicase ASCC3 as ribosome protectors.

Past

• Invented an RNA-programmable Argonaute - https://www.ncbi.nlm.nih.gov/pubmed/29531059 - with an advantage of having the ability to specifically edit posttranscriptionally modified RNAs.

• Evolved yeast to become more tolerant of n-hexanol - https://www.ncbi.nlm.nih.gov/pubmed/29619086 - to increase yields producing medium-chain alcohols.

Schaffer Lab

Engineering regenerative and gene therapies.

Recent

• Reviewed the toolkit to reduce immunological responses to adeno-associated virus (AAV) delivery vehicles. https://www.ncbi.nlm.nih.gov/pubmed/30807882

Past

• Invent a delivery vehicle (rAAV2- retro) to specific mapping of projection neurons- http://www.cchem.berkeley.edu/schaffer/2016%20Publications/Neuron.pdf - these neuron types are critical for computation between regions of the brain far apart.

• Invented a biomaterial platform to create large numbers of action-potential firing midbrain dopaminergic (mDA) neurons - http://www.cchem.berkeley.edu/schaffer/2017%20Publications/SciRep.pdf - where the neurons showed a 30-fold increase in viability versus 2D culture after implantation into rat striatum.

• Review of neural stem cells (NSCs) and how biomaterials can help study the role of biophysical inputs on the regulation of NSCs. https://www.ncbi.nlm.nih.gov/pubmed/29399646

Vance Lab

Studying the interactions between the innate immune system and pathogens.

Recent

• Discovered a secreted ubiquitin ligase that inflammasome activation - https://www.ncbi.nlm.nih.gov/pubmed/30872533 - the work shows how pathogen-encoded enzymes activate the inflammasome, multiprotein system that initiate the innate immunity response.

Past

• Discovered two effectors (Lgt and SidE) that inhibit host translation to free up amino acids for the intracellular bacterial pathogen Legionella pneumophila. https://www.ncbi.nlm.nih.gov/pubmed/29166595

Tjian-Darzacq-Betzig Lab

Pushing the limits on visualizing cellular and molecular events to understand core biological mechanisms.

Past

• Discovered that alternative promoters (P1 and P2) can be differentially regulated across cell-types. https://www.mdpi.com/2073-4425/9/6/270

• Really great paper to create a tool to quantify CTCF and cohesion - https://www.biorxiv.org/content/10.1101/370650v1 - both proteins drive 3D genome architecture and are major regulator of topological associating domains (TADs).

Dillin Lab

Studying the genetic and molecular mechanisms that regulate aging and age-related disease.

Recent

• In Caenorhabditis elegans, study how the actin cytoskeleton changes over time - https://www.ncbi.nlm.nih.gov/pubmed/30133343 - showing decline at advanced age in the muscles, intestine, and hypodermis.

• In Caenorhabditis elegans, discovered that Wnt signaling supports a global response to mitochondrial stress from the nervous system to peripheral tissues. https://www.ncbi.nlm.nih.gov/pubmed/30057120

Past

• Discovered that mitochondrial perturbation turns on both the mitochondrial unfolded protein response (UPRmt) and the heat stress response mediated by dve-1 and hsf-1. https://www.ncbi.nlm.nih.gov/pubmed/27610574

Fletcher Lab

Visualizing and engineering cellular mechanics.

Past

• Studied KRAS’s (one of the three horsemen of the undruggable genome) interaction with the plasma membrane - https://www.ncbi.nlm.nih.gov/pubmed/30559287 - using synthetic membranes, found that KRAS and the oncogene, RAF1 mainly interact via negatively charged lipids.

• By creating a model of antibody-opsonized cells, discovered that phagocytosis is significantly reduced when antigen height positions antibodies more than 10 nm from the cell surface. https://www.ncbi.nlm.nih.gov/pubmed/29958103

Zoncu Lab

Understanding how nutrients regulate growth and homeostasis.

Recent

• Important work especially for diet and longevity understanding how mTORC1 interacts with the lysosomal membrane - https://www.ncbi.nlm.nih.gov/pubmed/30061680 - using dynamic imaging to discover that Rag-Regulator cycling controls mTORC1 signaling.

• Overview of lysosomes and their role as cellular signaling centers. https://www.ncbi.nlm.nih.gov/pubmed/30602725

Past

• Understanding how cholesterol in the lysosome activates mTORC1. http://science.sciencemag.org/content/355/6331/1306?ijkey=/RrGhcIElR42k&keytype=ref&siteid=sci

Arkin Lab

Discovering and engineering evolutionary design principles of cellular networks and populations.

Recent

• Used random barcode transposon sequencing (RB-TnSeq) to measure the fitness of thousands of genes at the same time to find new enzymes involved in L- and D-lysine metabolism. https://www.biorxiv.org/content/10.1101/450254v2.abstract

Past

• Created a framework to understand deterministic and stochastic processes in complex microbial populations - https://www.pnas.org/content/111/9/E836.short - work is very similar to the inventions forming the basis of Boost Biomes.

Miller Lab

Developing and using molecular tools to study neuroscience.

Recent

• Invented new voltage-sensitive fluorescent reporters. https://chemrxiv.org/articles/Long-wavelength_Fluorophores_for_Voltage_Sensing/7663124

• Invented a method, fluorescence lifetime-based approach (VF-FLIM), to quantify transmembrane potentials at a single-cell level. https://www.biorxiv.org/content/biorxiv/early/2019/01/14/519736.full.pdf

Past

• Created new fluorescent voltage-sensitive dyes, sulfonated rhodamine voltage reporters (sRhoVR), compatible with mouse brains to image intact brains in vivo. https://pubs.acs.org/doi/pdf/10.1021/acscentsci.8b00422

Raulet Lab

Investigating the mechanisms of natural killer cells.

Past

• Discovered that cGAMP from tumor cells leads to STING activation in immune cells located in the TME producing interferons that activate NK cells. https://mcb.berkeley.edu/labs2/raulet/sites/mcb.berkeley.edu.labs2.raulet/files/u7/%20%20%20%20181016MarcusImmunityTumorcGAMP.pdf

• Discovered that tumor-derived colony-stimulating factor-1 (CSF-1) is necessary and sufficient for macrophage induction. https://mcb.berkeley.edu/labs2/raulet/sites/mcb.berkeley.edu.labs2.raulet/files/u7/elife-32919-v2.pdf

Bustamante Lab

Pioneering the use of single-molecule biophysics.

Recent

• Developing a theoretical framework to understand the efficiency of molecular machines at far from equilibrium conditions - https://www.ncbi.nlm.nih.gov/pubmed/30867295 - focusing on the folding and unfolding of single DNA hairpins.

Past

• An incredibly exciting paper using single-molecule fluorescence spectroscopy to show the link between a single enzyme and the heat it releases in a reaction. https://www.ncbi.nlm.nih.gov/pubmed/25487146

Hockemeyer Lab

Studying and engineering telomerase and telomeres.

Past

• Important study of TERT promoter mutations (TPM) - https://www.ncbi.nlm.nih.gov/pubmed/28818973 - discovering they promoted genomic instability and consequentially tumorigenesis.

Keasling Lab

Metabolic engineering for energy and health.

Recent

• Studied how membrane viscosity affects metabolic respiration - http://science.sciencemag.org/content/362/6419/1186.abstract - inventing a method to titrate inner membrane viscosity of Escherichia coli across a 10-fold range in order to understand the effect on metabolism.

• Overview of how engineering polyketide synthases (PKS) can extend lifespan through mimicking caloric restriction. https://pubs.acs.org/doi/abs/10.1021/acsomega.8b01620

Past

• Key overview of engineering modular PKSs to generate existing and new chemical matter. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655351/

Nomura Lab

Using chemoproteomic platforms to pursue the undruggable genome.

Recent

• Using activity-based protein profiling(ABPP) to elucidate the mechanism of the anti-cancer natural product, nimbolide. https://www.biorxiv.org/content/10.1101/436998v1

• Using ABPP to identify molecules that interactant with cysteine specifically for the E3 ligase, RNF4 in order to generate small molecules that can use RNF4 to degrade target proteins. https://www.biorxiv.org/content/10.1101/439125v2

• Mapping out the targets of the natural product, parthenolide in human breast cancer cells. https://www.biorxiv.org/content/10.1101/550806v3

Past

• Chapter giving an overview of using chemical biology to understand natural product mechanisms. http://nomuraresearchgroup.com/wp-content/uploads/Nomura-Maimone-2018-CTMI.pdf

Doudna Lab

Studying the fundamental role of RNA in the cell and health and pioneering the use of emerging new molecular tools.

Recent

• Relying on metagenomic analysis to identify a new gene editing effector, CasX - https://www.nature.com/articles/s41586-019-0908-x - however, the most important part of this research is the use of cryo-EM to characterize CasX at an unprecedented speed.

• Showed that an integrase system with Cas1 alone can mediate DNA integration into CRISPR arrays. https://www.ncbi.nlm.nih.gov/pubmed/30709710

Past

• Published an interesting paper showing anti-CRISPR (Acr) proteins inhibit Cas9 activity through prevent specific protein residues important for binding DNA. https://www.ncbi.nlm.nih.gov/pubmed/30595438

• Based on metagenomic analysis, use a CRISPR system from archaea (Cas14) to implement single-nucleotide polymorphism genotyping - https://www.ncbi.nlm.nih.gov/pubmed/30337455 - the analysis suggests that CRISPR may have a single evolutionary source selected overtime from the arms race between microbes and their predators.

• In a high-throughput manner, screen for inhibitors of Cpf1 editing. https://www.ncbi.nlm.nih.gov/pubmed/30190307

• To achieve cell-specific gene editing, created a method to engineer S. pyogenesCas9 with asialoglycoprotein receptor ligands (ASGPrL) - https://www.ncbi.nlm.nih.gov/pubmed/29668265 - allowing delivery into cells with the corresponding receptor.

Nogales Lab

Pioneering the use of cryogenic electron microscopy to understand the cell and molecular function.

Recent

• Interesting review of polycomb repressive complex 2 (PRC2) - https://www.ncbi.nlm.nih.gov/pubmed/30451485 - the only methyltransferase specific to histone H3 lysine 27 (H3K27) inducting the repressive trimethylation mark.

• Exciting use of cryo-EM to understand how TFIID, transcription pre-initiation complex, recognized promoter DNA. http://science.sciencemag.org/content/362/6421/eaau8872.full?ijkey=n1zIXWJX9ahXE&keytype=ref&siteid=sci

Past

• Great review on the power of cryo-EM - https://www.sciencedirect.com/science/article/pii/S0092867417313259 - with the long-term vision of creating “3D representations of the entire proteome and … [as] snapshots of the interaction networks underlying cellular functions.”

• Using cryo-EM to understand the human transcription factor IIH (TFIIH), an important part of transcriptional initiation - https://www.ncbi.nlm.nih.gov/pubmed/28902838 - important value to understand transcription and provide a pathway to specifically drug core complexes.

Rape Lab

Studying ubiquitin and its role in development and health.

Recent

• In Science, discovered a QC pathway naming it dimerization quality control (DQC) and finding an E3 ligase important for the function of the neural crest and neurons. https://www.ncbi.nlm.nih.gov/pubmed/30190310

Past

• Discovered that calcium signaling activates an ubiquitin ligase, CUL3, important for neural crest specification linked to autism, hyper-tension, and schizophrenia. http://mcb.berkeley.edu/labs/rape/reprints/McGourty_Cell_2016.pdf

Dueber Lab

Tools to engineer metabolism.

Recent

• Inventing EvolvR - http://dueberlab.berkeley.edu/wp-content/uploads/Halperin_2018_Nature.pdf - to continuously diversity any genetic loci; important for development of new agricultural traits, TCRs, and antibodies.

Past

• Creating a framework to engineer yeast to breakdown xylose - http://dueberlab.berkeley.edu/wp-content/uploads/Latimer_et_al-2017-Biotechnology_and_Bioengineering.pdf - incredibly useful to recycle food waste into high value products.

Kumar Lab

Engineer mechanical and biophysical communication between cells and materials.

Recent

• Great overview on the physical effects of the microenvironment on stem cells - http://kumarlab.berkeley.edu/wp-content/uploads/2019/07/NatMat19.pdf

Past

• Defining the relationships between stress fibers and cell patterning - http://kumarlab.berkeley.edu/wp-content/uploads/2017/05/Kassianidou2017.pdf - relying on computational and genetic methods.

Lee Lab

Using bionanoscience, biophotonics, and quantum nanoplasmonics for living cell imaging, cell reprogramming, and diagnostics.

Recent

• A legendary lab pioneering the use of microfludics and recently organoids; great overview on organ-on-chips - https://onlinelibrary.wiley.com/doi/full/10.1002/adhm.201701488

Healy Lab

Design of bioinspired materials.

Past

• Inventing a modular organ-on-chip system - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595286/ - to help scale up the screening tool.

• Great overview on the usefulness of biomaterials for treating cardiac disease - https://www.sciencedirect.com/science/article/pii/B9780128035818102486?via%3Dihub

Marletta Lab

Studying protein function and enzyme reaction mechanisms.

Recent

• In a tour de force type of paper, using cryo-EM to determine the structure of mammalian nitric oxide synthase - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4156747/

• Using biochemical methods to characterize Cyg11, a gas-responsive soluble guanylate cyclase in C. reinhardtii - https://pubs.acs.org/doi/10.1021/acs.biochem.9b00190 - important to understand how cyclases convert GTP to cGMP. 

Schepartz Lab

Creating genetically encoded materials.  

Recent

• UC Berkeley got a steal by picking by Schepartz; recently using fluorescence correlation spectroscopy (FCS) to understand how cell-penetrating peptides (CPP) move across the membrane - https://pubs.acs.org/doi/full/10.1021/acscentsci.8b00446

• Great overview on engineering ribosomes to generate foldamers (customer cyclized peptides) - https://www.nature.com/articles/s41557-018-0036-5

Maharbiz Lab

Designing brain interfaces.

Recent

• Inventing neural dust - https://arxiv.org/abs/1307.2196 - to create a brain-machine interface relying on ultrasound instead of electro-magnetic waves forming the basis of Iota.

Best,

Josh