An illustration of scientists in white lab coats celebrating on an unfolding reel of different TS digest issues.

TS Digest Turns One

As we reflect upon our first year, we seek reader feedback to continue on a path of success.

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Modified from ©, Nadezhda Fedrunova; gleolite; solargaria

Time flies! It seems like yesterday that I wrote my first editorial for the launch of the TS digest last year, describing it as the literary equivalent of a fine dining tasting menu. Our goal behind curating this interactive, bite-sized digital magazine was to provide you, our readers, with refreshing content—short articles, brief podcast episodes, videos, infographics—for when you need a quick science break from your busy day.

It has been overwhelmingly exciting to see our readers warmly welcome the TS Digest into their devices with an insatiable appetite for short-form articles. Along the way, we introduced new columns: Epic Fail, where researchers share their lab disaster stories; Just Curious, where we find an expert to answer a common biology question; and Science Snapshot, where we cover the story behind a scientific image. While you enjoyed our stories on diverse topics, from endogenous psychedelics to designer peptoids that pop viral membranes, you especially loved these novel content formats.

My favorite aspect of the TS Digest is that it offers us an opportunity to interact with our readers. Every month, with the launch of a new issue, I excitedly await reader feedback; a special thanks to the hundreds of readers who shared their thoughts on editorials, submitted their embarrassing Epic Fail stories, or asked poignant Just Curious column questions in the past year. Being in lock step with our readers has allowed us to keep the TS Digest alive, customizing every issue to satisfy your cravings. 

As we celebrate one year of TS Digest, I once again look to you all to guide us on how to best serve you. Are there certain topics you would like to see more of? Do you have ideas about new content types that we should cover? Would you enjoy more than one TS Digest issue per month? We look forward to your input to keep the TS Digest community going strong.

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Cartoon of a scientist kneeling over a broken sample tube on the floor.

Crushing ChIP Like Never Before

A wayward lab chair ended three days of work in a single footfall for Elinne Becket.

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Modified from ©, gmast3r; robuart; AlonzoDesign; designed by erin lemieux

As a postdoctoral fellow in Peter Jones’s lab at the University of Southern California, I studied DNA methylation and nucleosome positioning in renal cell carcinoma tumors. For my project, I collected donated patient tumor samples and used chromatin immunoprecipitation (ChIP) to study changes in their histone patterns. This was in the early days of ChIP, so there weren't kits that worked for my samples, and our in-lab protocol took about three and a half days to complete. 

A photograph of woman with brown hair smiling at the camera.
Elinne Becket, currently a microbial genomicist at California State University San Marcos, narrated her crushing mistake as a postdoctoral fellow.
Ciara Sanders

One day, as I finished the last elution at the end of this process, I dropped one of my samples. When I looked down and saw that the lid stayed closed, I breathed a sigh of relief. I started to step down to pick up the tube. Unfortunately, the chairs we used rolled at the slightest touch. As I shifted my weight, the chair rolled back, and my foot landed right on top of my sample. 

I was horrified. Luckily, I had planned to have extra replicates, so I didn’t ruin my whole experiment. However, I was mad at myself for wasting such a precious sample that someone was kind enough to let us use in our research. I don’t remember how my mentor reacted to the news, but I recall that my lab mates teased me for a couple of weeks about the accident, basically until one of them goofed, and the taunting transferred to a new target.

It still makes me cringe when I think about that incident. However, it serves as a good reminder to myself, and now my students, that mistakes happen, but steady lab hands and preparation will prevent most of them from occurring. What’s more important is that I learn from my mistakes so that they only happen once.

This interview has been edited for length and clarity.

A photo of a scientist placing a sensing lid onto a 96-well microplate before attaching Resipher.

Demystifying Cell Culture Through Oxygen Analysis

Walker Inman explains the importance of monitoring cells in culture.

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Lucid Scientific

Learn More

With a track record of invention and translating technology into practical solutions, Walker Inman continues to drive innovation in the life sciences field. Inman is currently the cofounder and CEO of Lucid Scientific Inc., a company that develops cellular analysis tools.

In this Science Philosophy in a Flash podcast episode brought to you by Lucid Scientific, The Scientist spoke with Inman about the challenges of measuring oxygen concentration in cell culture and how his real-time oxygen monitoring technology, Resipher, overcomes these problems.

Learn more about Lucid Scientific and Resipher.

          headshot of Walker Inman

Walker Inman
Cofounder and CEO
Lucid Scientific Inc.

How do you monitor your cells when growing them in culture?

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Cluster of red, green, and yellow neurons

The Making of a Memory

Sheena Josselyn discussed how she uses optogenetic tools to bias, express, and erase memories in mice.

Image Credit:

Asim Rashid

Engrams are ensembles of cells that encode, store, and retrieve memories.1 Although conceptualized in the 1900s, scientists struggled to demonstrate their existence, but technological advances help shine a light on the elusive engram.2 Sheena Josselyn, a neuroscientist at the Hospital for Sick Children, uses optogenetics to study engrams.

     Photo of Sheena Josselyn
Looking to the future, Sheena Josselyn, a neuroscientist at the Hospital for Sick Children, said that she is excited to explore engram stability over time, memory orchestration across multiple brain regions, and factors that affect the quality of a memory.
Sheena Josselyn

How does an engram form?

We hypothesized that engrams selectively recruit more excitable cells. To test this, we infected a random population of neurons in the mouse hippocampus with a viral vector that expresses both excitatory and inhibitory opsins that respond to different wavelengths of light.This enabled us to turn the same cells on or off throughout an experiment. 

Shortly before we trained mice to associate a context with an aversive foot shock, we activated these cells with light to nudge them into an excitable state. Then to label the memory engram, we used another approach that fluorescently tags cells activated during the behavioral task. Under the microscope, we saw an overlap in fluorescence, suggesting that optogenetically activating the neurons biased them towards becoming part of the memory engram. One day later, we optogenetically silenced the engram during a memory retrieval task and observed a big memory deficit. 

How have optogenetic tools advanced memory research?

Optogenetics has been a game changer. It allows us to answer questions we’ve been dreaming about for years. Newer opsins facilitate more sophisticated experiments that answer these questions in finer detail. We’ve used new optogenetic tools to explore rewarding and false memories and the linking and generalization of memories occurring close in time.4-7

This interview has been edited for length and clarity

Conceptual gene therapy illustration with 3D multicolored adeno-associated viruses in the foreground and multicolored DNA strands in the background.

Quality Control for Cell and Gene Therapy

An orthogonal method to cell culture speeds up testing for AAV and lentivirus vectors.

Image Credit:

©, Dr_Microbe

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          Multicolored vials with product boxes in the background representing laboratory testing kits.
Testing for replication competent AAV and lentivirus is a critical component of gene therapy best practices. Orthogonal testing kits provide researchers with a faster, quantitative option for superior quality control.

Cell and gene therapy holds tremendous potential for treating a wide range of diseases and disorders. Researchers routinely use viral vectors to shuttle and integrate genes of interest into cell genomes, among which the most frequently used are lentivirus and adeno-associated virus (AAV) vectors.1 Even though these viral vectors are designed not to replicate, researchers must nevertheless adhere to fundamental safety and quality control considerations to minimize the risk of exposure and adverse events if viral particles inadvertently infect cells and begin replicating after administration. As a result, cell and gene therapy researchers must routinely test for replication competent virus (RCV) according to well-established regulatory authority requirements.2

The most common method for evaluating replication competency of lentivirus and AAV vectors is through serial passaging of virus in cell culture lines and subsequent identification of viral particles in the supernatant using molecular assays. While considered tried and true, this approach is labor and resource intensive and can take over a month to complete. As a result, researchers face significant turnaround time challenges that create bottlenecks and impede workflows.

Researchers engaged in cell and gene therapy research and development seek novel, robust, and highly sensitive technologies as alternatives to traditional RCV testing protocols. For example, Bio-Rad’s Vericheck ddPCRTM replication competent lentivirus and AAV kits provide a quantitative, highly specific, cost-effective, validated, and rapid solution for routine RCV evaluation. With the ability to cut testing time down to under eight hours and produce results that are 99.9% specific, this approach allows cell and gene therapy researchers to meet rigorous regulatory requirements and take quality control due diligence to the next level.

Learn more about replication competent lentivirus and AAV testing.

What challenges do you face when performing quality control testing?

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Pieces of cheddar cheese.

How Microbes Craft Cheese Flavors

Bacterial strains compete and cooperate to make cheddar cheese tasty.

Image Credit:

©, Michelle Lee Photography

Humans mastered the art of cheese fermentation over thousands of years. Although researchers knew that some bacterial species were key to cheesemaking, they knew little about the microbial community interactions that occurred as milk turns into cheese.1 

After conducting a year-long experiment, researchers led by Ahmad Zeidan, a bioengineer at Chr. Hansen (now Novonesis), cracked how these microbial interactions affect cheese flavor formation.2 Their findings, reported in Nature Communications, could help cheesemakers finetune cheddar characteristics. 

The team chose cheddar cheese as a model system because its composition of 25 to 30 bacterial strains provided an intermediate level of microbial complexity to work with, Zeidan explained. They then assessed the effects of specific bacterial strains on cheese flavor by removing either a single strain or a group of strains from the starter culture. 

The presence of Streptococcus thermophilus was essential for the growth of the Lactococcus bacterial population. Metatranscriptomic and metabolic modeling of controlled milk fermentation experiments revealed that S. thermophilus acts as a key amino acid donor to the Lactococcus community, alleviating nitrogen limitations that may occur during cheese ripening.

Metatranscriptome analyses also revealed that one Lactococcus cremoris strain made cheddar taste good by limiting the formation of compounds that, when in excess, lead to off flavors.3 When the team took a closer look at the Lactococcus community, they found that competition between L. cremoris and another Lactococcus strain drove the formation of these compounds.

“This work advances the field [by] figuring out what needs to be done to make cheese taste the way we want it to taste,” said Maria Marco, a microbiologist at the University of California, Davis, who was not involved in the research. “It [also] shows the complexity of microbial environments. We're not just talking about different species, but different strains of the same species interacting with each other.”  

  1. Button JE, Dutton RJ. Curr Biol. 2012;22(15):R587-R589.
  2. Melkonian C, et al. Nat Commun. 2023;14(1):8348.
  3. Calbert HE, Price WV. J Dairy Sci. 1949;32(6):515-20.
A woman feels discomfort while she is thirsty (left), but she feels refreshed and rejuvenated when she has her first sip of water (right).

Why Does Drinking Water Feel so Rewarding When One is Parched?

With a thirst for knowledge, scientists delve into gut-brain pathways to understand liquid rewards.

Image Credit:

Modified from ©, Denis Novikov, Aleksei Morozov, Putthiphon Chuenwattana; designed by Erin Lemieux

In the sweltering heat of a summer afternoon, few things are more rewarding than a cold glass of water. The first sip might even elicit an exaggerated sigh of relief. Why does something as simple as drinking water immediately feel so refreshing?

          Headshot of Yuki Oka.
Yuki Oka, a biologist at the California Institute of Technology, studies how the brain controls behaviors toward homeostatic regulation, particularly fluid regulation, by balancing water and minerals.
California Institute of Technology

Our bodies are wired to seek ways to fulfill basic needs, like quenching thirst, and come with an internal reward system when we maintain fluid balance. Thirst neurons in the brain signal to our bodies with an unmistakable cue: a parched, scratchy sensation in the back of the throat.1,2 The first gulp of water feels euphoric because the brain responds with a rush of dopamine, a feel-good neurotransmitter, even though it takes 15 to 30 minutes for water to dilute the bloodstream.

“The concept of satiation or rehydration and the rewarding feeling are separable components,” explained Yuki Oka, a biologist at the California Institute of Technology. The body knows when thirst is truly satiated based on multiple sensory pathway signals. 

Oka’s group identified two types of thirst satiation neurons. One activates after gulping water and releases dopamine, while the other responds to the gut monitoring changes in water concentration.3 Activating both neuron types is necessary to fully quench thirst and feel like a liquid reward.4 When Oka’s team bypassed the signals induced by gulping and administered water directly to the gut, dopamine wasn’t released.

Now, with each sip of cool, refreshing water, imagine a mini celebration between the body and the brain in a toast to staying hydrated.

What makes you curious? Submit a question for us to answer in future “Just Curious” columns.

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  1. Zimmerman CA, et al. Nature. 2016;537(7622):680-684. 
  2. Martins PR, et al. Rev Esc Enferm USP. 2017;51:e03240.
  3. Augustine V, et al. Nature. 2018;555:204-209.
  4. Augustine V, et al. Neuron. 2019;103(2):242-249.e4.
On the left, a diagram of a fetus and placenta inside the abdomen of a pregnant person, on the right, a pink mitochondrion.

Mitochondria: The Powerhouse of the Placenta

Scientists seek citizens’ help to survey placental mitochondria in complicated and healthy pregnancies.

Image Credit:

Modified from ©, KKT Madhusanka; ©, RFBSIP; designed by Erin Lemieux

While the placenta only lasts about nine months, dysfunction of this temporary organ can have long-term consequences for the health of the mother and baby.1 “If the fetus doesn't get everything it needs, the baby's born, but it just doesn't have the resilience that it would otherwise have,” said Rohan Lewis, a placental physiologist at the University of Southampton. Despite this organ’s importance, the mechanisms that contribute to the proper function of its cells are not well understood.

          A black and white scanning electron microscopy image of cells within the placenta.
Cells of the placenta separate maternal blood (top left) from the fetal blood (bottom right).
Rohan Lewis

To help close this knowledge gap, Lewis, along with placenta researcher Michelle Desforges at the University of Manchester, and bioinformatician Michele Darrow at the Rosalind Franklin Institute, launched a citizen science initiative to characterize the crucial internal machinery of placental cells.

In the present study, they will analyze cells in the outermost layer of the placenta, which mediates the exchange of maternal nutrients and fetal waste products by using samples donated by women with healthy pregnancies and women who experienced complications like preeclampsia.

“These cells are metabolically really active,” said Lewis. “And cells that are metabolically active need a lot of mitochondria.” The researchers want to determine how the numbers, sizes, and structures of the mitochondria might link to the abilities of the cells, and by extension, the placenta as a whole, to function properly.

By using scanning electron microscopy, the researchers constructed three-dimensional images of the placental cells and the mitochondria they contained. Now, said Lewis, “We've got this gap where the technology for imaging is leaps ahead, but our capacity to analyze that data is still way behind.”

The team turned to the collective power of citizen scientists to overcome this challenge. Participants in the Placenta Profiles project will identify and tag mitochondria in this enormous bank of microscopy images, enabling researchers to assess mitochondrial dynamics and train machine learning models to perform this identification task in the future.

Are you working on a citizen science project?

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