Milka Kostic

Cell Chemical Biology: Home of Exciting Chemical Biology.

Table of Content Wish List“An Atomic Resolution Map of a Working Cell” (Bridget Carragher)“A Universal Method for Compound Target Identification” (James K. Chen)“A Lego Kit of Biosynthetic Modules for Secondary Metabolite Production” (James K. Chen)“Quantitative Sequencing of Carbohydrate Modifications on Proteins” (James K. Chen)“Evolution of Smart Materials” (Jason Chin)“Mars Needs Histones” (Andrea G. Cochran)“Metabolomic Engineering: A Systems Biology Application of Large Scale Chemical Biology” (Craig M. Crews)“Antibiotic Resistance Conquered” (Zixin Deng)“Single Microbe as a Drug Bank: Opening the Treasure Hidden in the Crypts” (Zixin Deng)“Rapid Experimental Evolution of New Antibiotics” (Elke Dittmann)“A Synthetic Self-Replicating Proto-Cell” (Michael Famulok)“Synthesis of a Complete, Universal T Cell Genome Optimized for Engineering” (Michael Fischbach)“High Coverage Proteomics Dataset Collected Using a Smart Phone” (Jason Gestwicki)“Combined Genomic and Metabolic Profiling of Tumors Leads to the Development of an Efficient Personalized Targeted Therapeutic Approach” (Eyal Gottlieb)“Chemical Mind Biology” (Masatoshi Hagiwara)“Mirror Image Protein Synthesis” (Michael C. Jewett)“Incipient Speciation in a Synthetic Microbial Ecosystem” (Gerald F. Joyce)“Continuous Monitoring of Single-Cell RNA Expression during Hepatic Regeneration” (Gerald F. Joyce)“Discovery of Compounds that Prevent Neurodegeneration” (Thomas J. Kodadek)“Small Molecule PCR” (Luke Lavis)“First Fully Synthetic Living Cell” (Edward Lemke)“Ten Color Optogenetic Control of a Flying Drosophila” (Edward Lemke)“Small Molecule Cocktail Alters Cell Fate between Growth and Differentiation” (Jun Liu)“Metabolomic Engineering: A Systems Biology Application of Large Scale Chemical Biology” (Wen Liu)“Biology from Omic Landscape to Molecular Details” (Minkui Luo)“Precision Medicine: Localized Restoration of Chemical Imbalance in Disease Brain States” (Milka Kostic)“Single Cell Proteomes Reveal Disease and Drug Biomarkers in Humans” (Timothy J. Mitchison)“Nanomolar Affinity, High Selectivity Binding Partners for Any Biomolecule in 1 Day for under

A Shout Out to Chemical Biology, a Multidisciplinary Field Par Excellence

100” (Timothy J. Mitchison)“Error-free Mutation Repair in Human Eggs (or .…Neurons)” (Timothy J. Mitchison)“Accurate Prediction of Protein Sub-cellular Localization across a Newly Sequenced Genome” (Timothy J. Mitchison)“On-Chip Measurement of 1000 Urine Biomolecules Allows Accurate Diagnosis of Early Stage Cancers” (Timothy J. Mitchison)“New Probes for Non-invasive Imaging of Mycobacterium tuberculosis in Latently Infected Humans” (Valerie Mizrahi)“A 2 Week Cure for Tuberculosis” (Valerie Mizrahi)“Visualizing Metallation and Mismetallation of Proteins in Live Cells” (Elizabeth M. Nolan)“Small Molecule Inhibitors of Muscle Atrophy and Memory Loss in the Aging Male” (Randall Peterson)“Polyketide Synthesis and Elaboration by a Remodeled Translation Apparatus” (Alanna Schepartz)“Reprogramming the Cellular Glycome Based on Rapid Glycan Sequencing and Synthesis” (Peter Seeberger)“Protein PCR” (Kevan Shokat)“De Novo Evolution of Entirely New Catalytic Function by Protein Enzymes” (Scott K. Silverman)“Biochemistry of First Living Isolate from Mars” (Brent Stockwell)“Rationally Designed Kampo Medicine” (Motonari Uesugi)“A Success Story on the Discovery and Development of Novel Antibiotics for the Clinical Treatment of Multi-Drug-Resistant Pathogens” (Tilmann Weber)“A Small-Molecule Ligand for Every Protein in the Proteome” (Eranthie Weerapana)“Highly Potent, Selective and Non-protein Binding Small Molecules Targeting RNA” (Herbert Waldmann)“Small Molecules as Big Players in Immuno-Oncology” (Herbert Wladmann)“Bioinformatic Tools to Extract More Information out of the Plethora of Primary Data” (Wolfgang Wohlleben)“Chemical Biology of the Gram-Negative Envelope; In Particular, How to Breach It with Small Molecules” (Gerard D. Wright)“Combinatorial Biosynthesis of Polyketides and Non-Ribosomal Peptides Comes True” (Wenjun Zhang)

Voices of Chemical Biology: Charting the Next Decade

Chemical biology is one of those fields that needs a bit of explaining. It is definitely a subfield within chemistry and at the same time it is now clear that it is an emerging discipline in both biology and translational research. It straddles the chemistry-biology-medicine continuum more effectively and better than any other named research endeavor (http://www.sciencedirect.com/science/article/pii/S1074552114002543).Having said that, I recognize that some will not be as convinced as I am, and as the editor of one of the most visible chemical biology journals, I spend a good amount of time thinking about what Cell Chemical Biology can do to change the perceptions and solidify the role of chemical biology as a major bridge between chemical, biological, and medical sciences. This is, of course, a very tall order, but I know that the journal, its editors, our editorial board members, authors, reviewers, and readers are bold and adventurous and sense that the community is heading in this direction.Some steps we take are huge, like making a decision to re-launch the journal as Cell Chemical Biology and better position ourselves as a basic biology journal while not relinquishing our role as a basic chemistry journal (http://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(16)00002-7). Or shifting our scope and interests towards many of the fields in which the impact of chemical thinking and a chemical way of doing things is starting to be the norm, helping the fields progress at an accelerated rate. Some of those fields include cancer research, metabolism and physiology, microbiome and microbiology, systems and synthetic biology, and drug discovery and development, and they are all represented in Cell Chemical Biology: Best of 2016, a free to access and free to download collection of the most read papers we published last year (http://info.cell.com/best-of-cell-chemical-biology-2016).I encourage you to take a look at this collection as it provides a nice overview of the diversity of research ideas and approaches that reflect the breadth of chemical biology. The field itself, however, is far more innovative and productive than one journal can ever hope to cover, so in order to promote and showcase some of the chemical biology stories that have been published in other journals, we decided to launch the Cell Chemical Biology Call.We borrowed the name and the format from Cell Systems, one of our sister journals,. For them, the Call was an invitation to their community to help the journal define the basic principles of an exceptionally multidisciplinary and quickly evolving field such as systems biology and to discuss newly published papers that encapsulate those principles (http://www.cell.com/cell-systems/fulltext/S2405-4712(15)00193-3). Additionally, the Cell Systems Call offered a view into the future and where each of the ideas is heading.What struck me while considering the basic idea behind this format and reading some of the Cell Systems Calls, which are all published under the title “Principles of Systems Biology,” is how engaging these highlights are and how much interesting yet easy-to-digest information they offer. I also started noticing parallels between the two fields and some conceptual commonalities. Both systems biology and chemical biology are exceptionally broad and interface with a number of different, more established fields. They are also relative newcomers, and researchers in both fields have invested major efforts to carve out their scientific identities. This also means that both fields are vibrant and growing, with many early career researchers entering the arena using tools and strategies based on chemical or systems level thinking and asking the types of biological questions that can only be addressed using these new tools. Finally, and fundamentally, because both fields are multidisciplinary, they are perhaps more difficult and require more effort to define and explain.The Cell Chemical Biology Call will offer engaging glimpses of the vast array of chemical biology literature as well as providing insight into modern chemical biology thought and the future of the chemical biology field. Each Call is a brief 200 word summary that highlights the basic principles behind a recently published paper and an answer to the question “what next?” Unlike the Cell Systems Call, where anyone may submit their article, all the contributions to the Cell Chemical Biology Call are invited by the editors and they signal the types of questions we view as timely and relevant. We will also not shy away from highlighting stories that may seem tangential to chemical biology research interests if we feel that future directions would benefit from more chemical biology involvement.Three recent studies highlighted in the first ever Cell Chemical Biology Call fit these rough guidelines well, as they highlight a cell biology story in which the researchers find link between mitochondria and proteostasis, thus opening the need for new chemical tools to dissect this relationship further; a protein engineering story in which researchers develop a new class of enzyme-based “plug-and-play” biosensors; and a clinically relevant gut microbiome story in which researchers take a closer look at the fungal members of our microbiome and their metabolic and chemical diversity.I hope you take a look at “Principles of Chemical Biology: From MAGIC to Gut Fungi, via ”Plug-And-Play” Biosensors” (http://www.cell.com/cell-chemical-biology/fulltext/ S2451-9456(17)30101-0) and enjoy the inaugural Cell Chemical Biology Call. I also hope you take these highlights to be a call to action, a call to ask different and more provocative scientific questions, and a call to talk more frequently and perhaps even more passionately about what chemical biology is and what it can do to bridge the venerable fields of chemistry, biology and medicine.

Biasing Opioid Receptors and Cholesterol as a Player in Developmental Biology

We recently asked our Editorial Board members to answer the following question: “what paper would you like to read in the January 2026 issue of Cell Chemical Biology?” We received more than forty responses, and if you are interested in what our Editorial Board members came up with, you can read all of the titles in the editorial that accompanied our January 2016 issue (http://www.cell.com/ccbio/fulltext/S2451-9456(16)00002-7). The world cloud you see here will also hopefully help to orient you with respect to some of the big themes that were on the minds of those who answered our question.

Chemical Biology as a Driver of Innovation in Cancer Research and Drug Discovery

Every month the editors of Cell Chemical Biology bring you highlights of the most recent chemical biology literature. Our September 2016 selection includes the discovery of PZM21, a μOR biased agonist with minimal side effects, and the role of cholesterol in Hedgehog signaling pathway.

Our Advisors, Our Ambassadors, Our Editorial Board Members

Several months ago, as we were launching the Cell Chemical Biology Call, we took some time to explain why we believe that chemical biology epitomizes what a multidisciplinary scientific field is all about (http://www.cell.com/cell-chemical-biology/fulltext/S2451-9456(17)30104-6). It is a discipline that successfully operates within the chemistry-biology-medicine continuum, thanks to its multidisciplinary nature and the mindset that its members have.Cancer research is one of those areas where chemical biology efforts have made remarkable and real scientific and clinical contributions. Efforts in chemical biology laboratories have produced a range of small molecules that are making a difference in the clinic today. Probably the most prominent example of such a compound is imatinib, which targets the active sites of a number of tyrosine kinases, including—most importantly—Bcr-abl kinase, and whose success solidified the importance of targeting oncogene addiction in cancer drug discovery anticancer drugs.In addition to clinically important small molecules, chemical biology efforts have led to the development of a large number of chemical probes that are currently in widespread use in basic cancer biology, like JQ1, a selective inhibitor of the BET family of bromodomains, which was disclosed in 2010 (http://www.nature.com/nature/journal/v468/n7327/full/nature09504.html) and appears in close to 350 research articles based on a recent Scopus keyword search. The use of chemical probes in cancer biology has been so widely successful that chemical biologists recognize the need to educate those who use the tool compounds on both the benefits and potential pitfalls (http://www.cell.com/cancer-cell/fulltext/S1535-6108(17)30303-3).Given all this, we decided that the second special issue under the name Cell Chemical Biology should focus on cancer research and how chemical biology is pushing the boundaries of fundamental biology, technology, and clinical science.In general, the use of chemical biology in drug discovery has come of age, with a growing number of systems-level (omic) and cellular technologies in place to identify potential targets; phenotypic, targeted, and computational screens to identify compounds that impinge on disease states; and sophisticated methods to link compound activities and targets. Nowhere is the impact clearer than in cancer—an umbrella term for a myriad of disease states that all boil down to derangements in cellular pathways—where chemical biology offers technologies and molecules to develop precision medicine.For this special issue, we picked nine topics to elaborate on two main broad themes, one that revolves around the idea of chemical biology as a driver of technology development and the other that showcases how chemical biology is helping better understand basic cancer biology, leading to drugs.For the more technological aspects of chemical biology in the context of cancer research, we highlight the value of bridging medicinal chemistry and chemical biology efforts, as discussed by Plowright et al.; the discovery of new biomarkers using high-throughout screens as described by Williams et al.; and tumor organoids, including patient-derived cells, as drug screening platforms, the focus of the review by Weeber et al.We transition the discussion from more technological to more basic science questions via a piece by Sharifnia et al. that focuses on rare cancers, as these represent a major area where technology and basic biology overlap to a great extent. We continue the special issue with a review by Hengel et al. highlighting the impact of chemical biology on the area of DNA repair research in the context of cancer and a piece by Ribich et al. discussing how chemical biology has been enabling cancer epigenetics research. Finally, we round up the special issue with three reviews that bring us closer to the clinical practice, with description of small molecule targets in immune-oncology by Dhanak et al., small molecule targets in cancer metabolism by Luengo et al., and targeted protein degradation as anticancer drug strategy by Cromm et al.Cancer research is vast, varied, and broad, as is the disease itself. This also means that the number of entry points and the impact chemical biology can have on cancer research are huge. We expect that, in the years to come, we will continue to see a growing interest among cancer biologists and clinicians in chemical biology and the other way around. As a journal, Cell Chemical Biology remains strongly interested in studies, reviews, and perspective in this area. We invite you to enjoy this special issue and to send us your innovative, provocative, and exciting cancer chemical biology stories. Our broad hope is that through multidisciplinary efforts like those highlighted in our special issue, we will be able to move the needle on cancer detection, diagnosis, and treatment.

From Powerful Review Articles to Research Breakthroughs

It is March, and the spring is definitely in the air here in Cambridge, MA, USA where Cell Press offices are located. If we said that, like the nature around us itself, Cell Chemical Biology editorial team is ready to spring into action that would be an understatement. Ever since the first issue of Cell Chemical Biology came out two months ago, we have been working hard to spread our message across the field of chemical biology and broader biomedical community to raise visibility and awareness of all the meaningful changes we are enacting. In return, we have been getting messages of support from the community and we are grateful and humbled by your enthusiasm and encouragement. That type of overwhelmingly positive feedback strengthens our confidence that re-launching Chemistry & Biology under the name of Cell Chemical Biology was the right thing to do for the journal and the field.One of the key groups of people that we have been interacting with a great deal throughout this process is our Editorial Board. We reached out to some members of the Editorial Board more than two years ago to get initial reactions on the idea to change the title to Cell Chemical Biology and these conversations really helped us shape the vision for the future. Additionally, people on our Editorial Board continued to provide us with the advice on more specific questions, such as suggestions for potential review article content and hot topics that would benefit from critical discussion. We plan to follow up on many of those and use interesting review type content to bring out a more complex flavor of the journal.Lastly, our Editorial Board Members actively participated in the process of Editorial Board expansion that we just went through. In preparation for relaunch we approached our existing Editorial Board to share that one of the big components of our strategy for making Cell Chemical Biology a success will be centered around rethinking our scope and the types of studies that we want to publish. In addition to “traditional” chemical biology studies that use chemical tools to perturb, visualize and measure properties of biological systems to build a better view of molecular mechanism and physiology, or those that are centered on biochemical mechanism and how to engineer it to increase chemical diversity of biosynthetic small molecules, we want Cell Chemical Biology to be home for studies that ask questions about metabolism and metabolites, as well as small molecule-protein and small molecule-nucleic acid conjugates especially those that push our appreciation for what specific post-translational and epigenetic modifications are doing. We are also excited about studies that combine the use proteomics, lipidomics, metabolomics, glycomics and other methods that offer systems level view of biology and transform those insights into a deeper mechanistic understanding. Even this expanded list it not all, as we see exciting work being done across the range of traditional biological disciplines, such as genetics, cell biology, developmental biology, neurobiology, immunology, as well as more recent areas of stem cell research and synthetic biology. We believe that chemical biology touches all aspects of biological research and we wanted to highlight this through opening up our scope.We also want our Editorial Board to reflect the diversity of science that the journal is interested in, and together with the Chemistry & Biology Editorial Board Members we worked hard to identify the type of expertise that we need in order to cover all the subject matter we were getting excited about, and find the diverse group of people to bring on board. Over the last several months we welcomed many new Editorial Board Members that have diverse scientific interests, and hail from all over the world. Additionally they also come from different stages in their scientific careers and we brought on board not only well-established senior scientists, but an exceptional group of up-and-coming next generation leaders.We are excited to have this fantastic group of advisors and ambassadors supporting Cell Chemical Biology. You may wonder what it is that our Editorial Board Members do, and it is a fair question. Our Editorial Board members don’t handle manuscripts and are not responsible for overseeing the peer review process or serving as the default reviewer pool. What we expect from our Editorial Board members is to be our ambassadors in their local and global scientific communities, and we count on them to promote the journal as a place for their colleagues and their field to publish exciting results. We depend on our Editorial Board Members to tell us what’s exciting in their area of research and what the future might bring, as well as to alert us if there are any changes to current best practices and standards in the field that we should know about. This helps us evolve our policies and criteria. Additionally, we rely on our Editorial Board Members to help us untangle complicated editorial decisions or adjudicate disputes that sometimes erupt between authors and reviewers.Editorial Board Members are our go-to group of scientists when we are thinking about new article formats, new features, or new initiatives and we look to them to point out not only exciting aspect of changes that we are thinking about but openly voice their concerns as well. For example, one significant concern that some members of our Editorial Board had during the relaunch process was that our emphasis on tackling difficult biological problems, problems that those in biology care deeply about will negatively impact the quality of chemistry we publish and rob us of our chemical heritage. We are still talking about this and have yet to reach the point where we feel this issue is put to rest, but as with other issues in the past these types of discussions help us understand the thinking and concerns in the field, and we are thrilled to have the Editorial Board that continues to challenge us to do right by the field.From day one, our goals for the journal have been lofty – we want Cell Chemical Biology to be home for the most exciting chemical biology research where chemical creativity meets biological complexity, and the two enhance each other to create insights into toughest scientific questions. We feel that having enthusiastic group of advisors and ambassadors on our Editorial Board will make achieving these goals easier and definitely more enjoyable.

RAF Inhibitors, Fishing Bacterial Transporters Out of Metagenomes, and Yeast-Based, Industrial Scale Production of Isoprenoids

For those who are working at the interface of chemistry and biology, chemical biology may seem like old news. Although most would agree that chemical biology is not yet a mature discipline like cell biology or physical chemistry, those who have dedicated their research careers to untangling the secrets of biological function using chemical approaches likely feel that chemical biology is a road well traveled. However, chemical biology is still in many ways a new kid on the block, and we, as editors of one of the leading journals dedicated to supporting the field, feel that it is our responsibility to help chemical biologists tell and hear each other’s stories as well as to help them place chemical biology contributions in the broader context.One way in which those thoughts are summarized, explained, and shared is through the review content that we publish. A useful review article is significantly more than a laundry list of facts: it is a snapshot of the thinking in the field delivered in a way that is both instructive for novices and deeply intellectually engaging for experts.Building on the description of a useful review article, an exceptional review article is one that not only informs and educates, but also provokes alternative ways of looking at a problem and inspires further research and discussion. A great review helps us not only to navigate the existing scientific literature and information overload, but leads us to discover new galaxies of scientific knowledge. We like to think that all of the review articles we publish are useful, and we hope that most of them are exceptional and play substantial roles in setting the research agenda for different fields we cover.Review articles are also a way in which editors engage more actively with the direction of the field. Most review articles published by Cell Chemical Biology are editorially commissioned, which means that the Editors decide on the topic for a review article and invite experts in the field to write it. Overall, there are many different ways in which editors identify a timely topic. Our ideas may crystallize while we browse through the existing literature, flip through meeting programs, watch webinars, or listen to talks at scientific conferences. We may get inspired by a newspaper article discussing a specific medical need, news of a drug approval, or a chance remark on social media. Often times, ideas pour in as we engage in conversations with members of the community or as we work with our authors and reviewers on shepherding the research papers submitted to Cell Chemical Biology through the peer review process. We also receive tips and suggestions from our Editorial Board members, who are our ambassadors and our eyes and ears in the community. Finally, some proposals are unsolicited and come to us through our presubmission inquiry process. These presubmission inquiries usually contain a brief explanation of why a certain topic would benefit from a synthesis and include a rough outline of the key points that the proposed review will cover, as well as a list of the key references that will be discussed.Regardless of where ideas and suggestions for our review articles come from, they all go through a process of careful evaluation before they become a formal invitation. Based on our experience, the best Cell Chemical Biology review articles are those that cover a topic of core current interest to chemical biologists, a topic that is undergoing rapid growth in terms of research interests, a scientific problem that requires major rethinking, a controversial issue with broad impact on the entire field, or a combination of all of these factors. Determining whether a topic we have in mind or a topic someone has proposed to us checks any of these broad guidelines is not trivial. It requires taking several steps back to look at the entire general area of research in which the given topic sits as well as related areas that may potentially be influenced by the discussion we publish. We consider both the quality and quantity of the research output that the potential review may cover because we want to publish reviews on topics that people actively care about. We also try to anticipate specific questions and issues that will be important points of debate and discussion in the near future, because great reviews don’t just appear—they are written by people who are passionate about carefully crafting their arguments and discussions and dedicated to delivering new galaxies of knowledge. This means that, on average, it takes about 8–12 months for a review article to go from idea to publication. Finally, we also take care to cover a variety of topics and issues that are of particular interest to chemical biologists and to invest effort into ensuring diversity in our review content. Unfortunately, this also means that we have to decline some of the unsolicited proposals to avoid overlap with what we already have in our review article pipeline.In the past, everyone on our editorial team has shared the responsibility for our review content. Although we enjoyed doing so, we felt that the journal, and the field, would benefit from a more focused and dedicated approach. Therefore, we have decided to expand our editorial team and bring on board a Reviews Editor who will lead our reviews strategy. We are pleased to announce that Michelle Arkin, Associate Professor of Pharmaceutical Chemistry and the Director of Biology at the Small Molecule Discovery Center at UCSF will serve as the Cell Chemical Biology Reviews Editor. Michelle’s research is focused on structure/function and chemical biology of allosterically regulated enzymes and protein-protein interactions (PPI). In addition, her lab has a strong interest in developing probes and drug leads to address mechanisms of neurodegeneration, cancer, and parasitic disease. Over the years, Michelle has co-authored several key review articles in the area of targeting PPI (see http://www.nature.com/nrd/journal/v3/n4/full/nrd1343.html and http://www.cell.com/cell-chemical-biology/fulltext/S1074-5521(14)00291-9) that stand as examples of the power of reviews to shape the direction of the field. We look forward to seeing what mark Michelle makes in her new role as our Reviews Editor.If you have an idea for a review, please email your suggestions to chembiol@cell.com.

Stem Cell Hydrogel, Jump-Starting Zika Drug Discovery, and Engineering RNA Recognition

Every month the editors of Cell Chemical Biology bring you highlights of the most recent chemical biology literature. Our October 2016 selection includes systematic structural, biochemical, and cellular characterization of B-RAF inhibitors; connecting bacterial transporters with their physiologically relevant ligands; and rewiring yeast metabolism for industrial scale production of isoprenoids.

That’s a Wrap!

Every month the editors of Cell Chemical Biology bring you highlights of the most recent chemical biology literature that impressed them with creativity and potential for follow up work. Our August 2016 selection includes a description of hydrogels with self-tunable stiffness that are used to profile lipid metabolites during stems cell differentiation, a look at whether we can find a drug repurposing solution to Zika virus infection, and an engineered RNA recognition motif (RRM).