A Platform for Efficient Establishment and Drug-Response Profiling of High-Grade Serous Ovarian Cancer Organoids

Authors used two types of cell culture media to successfully culture 55% of High-Grade Serous Ovarian Cancer (HGSC) surgical samples in long-term, passageable organoid cultures. Descriptive characterization via RNA-sequencing, copy number variation profiling, gene expression, and functional characterization via drug treatment all demonstrated a high level of concordance between organoid cultures and patient tumors.

I chose this publication because it showed a high degree of scientific candor. It presented the challenges of a hard-to-culture tissue and the less-than-perfect but still elegant solution of using two types of cell culture media to increase the capture of the HGSC sample population for use in vitro. As well, their threshold for success is a high one, and their experiments inform us of what customer expectations are in this field. This work exemplifies many of our core values, such as integrity and innovation.

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Sleep Regularity Is a Stronger Predictor of Mortality Risk than Sleep Duration: A Prospective Cohort Study

This research was about a cohort study examining sleep regularity, i.e. the consistency of sleep and wake up times. The authors found that sleep regularity was a stronger predictor than sleep duration for reducing mortality. Personally, I don't normally get 7 hours of sleep per night, but I sleep at regular times. It's a relief that science is showing that it might be ok if I can't get 7 hours of sleep a night! (Yes, I'm rationalizing my bad behavior).

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A CRISPR Screen of HIV Dependency Factors Reveals That CCNT1 Is Non-essential in T Cells but Required for HIV-1 Reactivation from Latency

Incurable diseases like HIV and cancer have always fascinated me. They seem like a puzzle that is waiting to be solved. How do you solve a puzzle with missing pieces though? This is where the field of synthetic biology steps in. Genome editing has opened a whole new avenue to explore the unknown. This article is one such example. The authors use CRISPR to find new biomarkers that can be exploited to target HIV latency. HIV is such a fascinating virus that evades all the current combined retroviral therapies. It does so by integrating its genome into our DNA and hiding the infected cell from being detected. There are two mechanisms currently under study: “shock and kill”, where latency reversal agents are employed to reactivate HIV from the latently infected cell and let our immune cells do their job, and “lock and block” where the latently infected cells are pushed deeper into latency so that the virus can never get activated. Both these mechanisms are an extremely clever way to cure the disease. We are so close, and yet so far due to the lack of biomarkers that define a latently infected cell. I believe the field of synthetic biology can find the cure for HIV and other incurable diseases one biomarker at a time.

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New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay

Spheroids and organoids are great tools to study tumor biology and screen compounds of interest. Unfortunately, these structures still lack key features of the tumor environment as the vasculature and the perivascular component. In this publication, the authors show for the first time a new strategy to induce high vascularization in both static and microfluidic assays. The authors induced vascularization of tumor spheroids using a novel technique based on adding fibroblasts sequentially to a pre-formed spheroid. This was demonstrated with tumor cell lines from kidney, lung, and ovarian cancer.

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Bioprinted 3D Outer Retina Barrier Uncovers RPE-Dependent Choroidal Phenotype in Advanced Macular Degeneration

Despite Age-Related Macular Degeneration (AMD) being accountable for ~8.7% of global blindness, there are few therapies to treat this retinal disease due to inadequate molecular insight. The main obstacle has been the limited availability of appropriate animal and cell culture systems that recapitulate key aspects of the disease in the human eye. In this paper, the authors addressed fundamental questions about retinal pigment epithelium-Bruch's membrane-choriocapillaris (RPE-BrM-CC) development in vivo and the lack of a human cell model for AMD and represents a tissue engineering breakthrough for using iPSC-derived models and drug screening.

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Programmable Multispecific DNA-Origami-Based T-Cell Engagers

Cancer immunotherapies based on different protein modalities are now established in clinical practice. However, the problem that plagues the design of these protein modalities is the spatial geometric arrangements of the domains that are used within the fused engineered antibody domains. To overcome this deficiency, the authors looked at implementing a novel DNA fabricating technology that is based on origami, the ancient Japanese art of folding a 2-dimensional piece of paper into a 3D object. What impressed me about this paper is that it combines artificial DNA structures with antibodies to improve the efficacy of immunotherapies. Beyond cancer immunotherapies, this platform technology can be adapted and optimized to develop novel products, such as cell separation cocktails and cell activation reagents.

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Pluripotent Stem Cell-Derived Model of the Post-implantation Human Embryo

Human reproduction is remarkably inefficient with ~60% of pregnancies failing during the first two weeks following fertilization. When implantation does succeed, the fertilized egg develops into three stem cell populations that give rise to the embryo itself, the yolk sac, and the placenta. To better understand cross-talk interactions between developing tissues and their effects on implantation, the team over-expressed transcription factors to drive the development of precursors that can generate the yolk sac and placenta.

This landmark study, which was established on years of work in mouse models, has several implications. Foremost it provides a model system to better understand the cellular dialogue in the developing embryo that ensures a successful pregnancy. Importantly, it provides a platform that can be used translationally to improve the chances of a healthy pregnancy, especially for couples undergoing IVF treatment.

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Reversible Photoregulation of Cell-Cell Adhesions with Opto-E-Cadherin

If you ever get a chance to see optogenetics in action, take it. Nature reported this technology as the Method of the Year in 2010 and since its realization within the neuroscience field, this nifty tool has been making its way across the biological spectrum. The authors here have developed a one-component photoreversible E-cadherin binding site to investigate cell-cell adhesions with blue light. Using a breast cancer cell line transfected with this tool, cell-cell adhesion modulation was shown to influence intracellular activity and overall behavior in 2D & 3D in-vitro workflows, as well as an in-vivo assay.

Out of all the great publications I read this year, this one is my favorite. My area of work predominantly lives within the PSC suspension culture world and as such I continually focus on cell aggregation - growth - dissociation - repeat. There are still many gaps in our understanding of each step so as I was reading this article my mind went buzzing with the possible mechanistic investigations and cell culture applications that the authors' work could lead to. On top of that, I greatly appreciated their use of quantification across multiple types of experiments. Indeed, a worthy read for all.

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Protein-Specific Signal Peptides for Mammalian Vector Engineering

Being a recombinant cell line-development Scientist, I know that getting good expression of single peptides or complex recombinant proteins in a mammalian expression system is challenging. Before we even start cell line development, we have to design a vector and find the right protein-specific elements that can improve protein expression. Advances in the synthetic biology field, particularly in DNA-sequence engineering, have significantly expanded opportunities to improve Chinese hamster ovary (CHO) cell expression vector design. This paper uses those techniques to find optimal signal peptide sequences for hard-to-express proteins and facilitates significant titer increases compared to the traditional approach. I am excited about trying these toolkits to design my vector and protein-specific signal peptides!

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Sequential Appetite Suppression by Oral and Visceral Feedback to the Brainstem

The authors of this publication show for the first time that mice in an awake rather than anesthetized state can be used for brain recordings during food consumption, showing how specific neurons in a region called the caudal nucleus of the solitary tract (cNTS) switch on during a meal to slow down and eventually end a feeding cycle.

This was an interesting publication for me as during my PhD, I studied how crucial it is to understand the parasympathetic system and how it regulates “rest and digest” functions. I am interested in GLP-1 and its role in gut and pancreatic glucose homeostasis and its use as the appetite-suppressing hormone mimicked by a new weight loss drug. I appreciated how the authors of this article highlight how it can regulate food intake by tracking stomach expansion, both naturally or by artificially stimulating these neurons by lasers. The research is a step forward in understanding abnormal feeding behavior, which could be particularly helpful in better understanding or helping obesity, anorexia, or bulimia.

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