Photograph of fermenters in a biorefinery in Brazil that produce bioethanol.

Not All Bacteria are Bad in Biofuel Production

Long seen as collective contaminants, some bacterial species actually promote bioethanol production.

Image Credit:

Felipe Lino

Biofuels like bioethanol provide energy alternatives to fossil fuels. Many processes that produce bioethanol involve fermenting yeast, so plant operators consider bacteria collectively as contaminants, but new research suggests that this is an oversimplification. 

In a study published in Nature Communications, a team of microbiologists demonstrated that while some bacterial species reduced bioethanol conversion, others improved its production.1 “That gives us more notes to play in terms of optimizing the process, because you can both add beneficial bacteria to the process, as well as try to avoid the detrimental bacteria,” said Morten Sommer, a microbiologist at the Technical University of Denmark and study coauthor. He and his group study how differences in the genetic and microbial composition of fermentation mixtures affects the product of interest yields.

To investigate how bacterial species affected bioethanol production, Sommer and his team sampled two biorefinery plants in Brazil at various points during fermentation over the production season. Using metagenomic analysis, the team identified two highly prevalent bacterial species, Lactobacillus amylovorus and Limosilactobacillus fermentum. They also observed that improved bioethanol production was associated with increased L. amylovorus while a high population of L. fermentum created acidic environments that reduced bioethanol production. 

The researchers found that out of the three strains of L. fermentum in the mix, only one detrimentally affected bioethanol production. Metabolic profiling demonstrated that this strain produced more lactate and no ethanol. Finally, the team explored conditions that promoted L. amylovorus and limited L. fermentum. Compared to L. amylovorus, all three L. fermentum strains grew better at 37° Celsius compared to 30°. 

Soo Rin Kim, a food microbiologist who studies yeast fermentation at Kyungpook National University and was not involved in the study, explained that improving fermentation processes is important to make the most of a limited resource. According to her, these bacteria provide a way to gauge the fermentation efficiency. “Later on, we’ll be able to figure out how to control those lactobacteria to improve the production,” said Kim.

  1. de Oliveira Lino FS, et al. Nat Commun. 2024;15(1):5323.
3D conceptual image of antibodies on a blue background.

Improving the Efficiency and Reliability of Fully Human Antibody Drug Development

Microfluidic technology enables high-throughput, droplet-based antibody discovery in fully human antibody mice.

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© istock.com, Svisio

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Antibody discovery research paves the way for new therapeutics. The search for the right antibody for a specific therapeutic application necessitates several iterations of antibody production and screening. During this process, researchers test and re-test the function of candidate antibodies, which is a resource-heavy and laborious endeavor. 

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Combining microfluidics single B cell technology with fully human antibody transgenic mice enables fully human antibody discovery.
Biointron

Traditional approaches, while tried and tested, present certain challenges. For example, hybridoma antibody screening, which involves fusing myeloma cells with antigen-activated B cells and then screening for target antibody production, is a multi-step and time-consuming process. Moreover, while traditional approaches use mice that have been genetically modified to produce human antibodies, these antibodies are not completely encoded by human genes and are, therefore, not considered fully human.

Microfluidic technology allows individual plasma B cells to be encapsulated in microdroplets and screened at high speed. This approach enables high-throughput, single-cell level analysis, ensuring researchers can screen vast numbers of antibodies while retaining high specificity and affinity for target antigens.

Best practices in antibody discovery also necessitate the production of fully human antibodies to ensure that scientists identify those that have high affinity and specificity for targeted human antigens. From a translational perspective, fully human antibodies have better safety and tolerance profiles because they are less likely to elicit an undesirable immune response in patients. 

As a result, scientists seek new and innovative options that enable safer, more effective, and streamlined antibody discovery workflows. Among such approaches is Biointron’s high-throughput fully human antibody discovery platform.  Combined with Cyagen’s HUGO-Ab™ fully human antibody transgenic mouse model, Biointron’s AbDrop™ technology enables microdroplet-based high-throughput screening of individual B cells by the millions. This approach halves the typical six-month discovery timeline to three months and offers an efficient and reliable next-generation platform for fully human antibody discovery.  

Learn more about safer and more efficient fully human antibody discovery. 

 

What is the biggest challenge you encounter when performing antibody discovery screening?

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Illustration of a blue piece of DNA with a red segment in its middle on a purple background. Blue and red segments that have been cut out surround the larger strand.

Splicing Fungal Genes Help Cells Change Shape

Candida albicans uses alternative splicing to morph into a filamentous form during fevers.

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The opportunistic pathogen Candida albicans grows in two forms: yeast and filament. The latter state contributes to the severity of infections, and elevated temperature promotes this morphological switch. However, the mechanisms that drive this transition are poorly understood. 

In a study published in mBio, a research team identified alternative splicing—the selective inclusion or excision of introns in a gene—as a contributor to filament formation in fever-like temperatures.1 Elucidating these pathways could offer novel strategies to target fungi during disease.

The team cultured a collection of mutants at 39 degrees Celsius and used microscopy to identify genes important to filamentation. They found that strains lacking genes relating to mRNA splicing failed to undergo this transition. Alternative splicing promotes adaptation to environmental changes; in fungi, the most common example of alternative splicing is intron retention.

To explore the relationship between splicing and filamentation, the researchers performed RNA sequencing on wild type C. albicans grown at 30 or 39°C. They noted that filamentous fungi induced by higher temperatures retained more introns. They also observed that intron retention decreased gene expression. 

The researchers investigated the effect of a splicing mutant on intron retention and gene expression. They observed that while elevated temperatures increased intron retention in wild type cells, the mutant strain retained more introns in genes. However, unlike in wild type cells, splicing mutants with more retained introns lost their gene regulatory ability. 

“Understanding why this is the case, understanding how these fluctuations in temperature are sensed and how those signals are transduced into sort of spliceosome function is certainly something that's interesting,” said Nicole Robbins, a mycologist and study author at the University of Toronto. 

“[The study] really added to this growing body of evidence that we have a very complex system of different layers of regulation which enable Candida albicans to react in a plastic or adaptable way to its environment,” said Sascha Brunke, a fungal microbiologist at the Leibniz Institute for Natural Product Research and Infection Biology.

Image of colored blobs comprised of individual dots. Each dot represents an immune cell and dots of the same color belong to the same cell type.

Charting the Human Immune Health Atlas

Researchers mapped the landscape of healthy immune cells from childhood through adulthood.

Image Credit:

Lucas Graybuck

Image of immunologist Claire Gustafson. She wears glasses and smiles at the camera while wearing a black shirt under a white lab coat.
Claire Gustafson, an immunologist at the Allen Institute for Immunology, works to unravel the mysteries of the immune system.
Erik Dinnel

Every individual’s immune system is distinct and changes over time, affecting their health and disease response. Recently, researchers mapped human immune cells to explore what defines a healthy immune system across different ages. 

“None of the [current immune-based] atlases were actually robust enough for our purposes,” said Claire Gustafson, an immunologist at the Allen Institute for Immunology, who led the Human Immune Health Atlas project to gain insight into the immune system’s complexity and diversity.

First, the team established their atlas criteria: a wide age range, more cells per person compared to other atlases, and a large pool of donors to capture population and individual heterogeneity. They used flow cytometry and single-cell RNA sequencing on more than 1.8 million cells from healthy male and female donors from the ages of 11–65 years old.

“While a lot of other available atlases have in the thousands of cells per person, when you look at rarer subsets, you’ll be missing those,” said Gustafson. “We actually did much deeper sequencing on a per sample level, where we got greater than 10,000 cells per person to build this map.”

From this vast cellular landscape, the researchers annotated 71 distinct immune cell subsets and generated a vibrant atlas depicting swaths of color. In the above image, each colored dot represents an immune cell, and dots of the same color belong to the same cell type, based on their gene expression.

The team observed changes in immune cell composition across the age groups. Building upon this atlas, described in a preprint, the researchers analyzed more than 16 million cells across the same immune cell subsets, discovering that T cells were primarily affected over time than other immune cells.1

“Deeply characterizing the immune system is going to be critical in designing better vaccines, age-specific therapeutics, and really gain insight into how changes might start and cause dysregulation,” said Gustafson.

  1. Gong Q, et al. bioRxiv. 2024.
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A black snake encircled with pattens of red and yellow spots, curled up against a black background.

How Do Snakes Fly?

Changing body shapes and coordinated wiggling provide lift and stability for gravity-defying reptiles.

Image Credit:

© istock.com, agus fitriyanto

For animals that live in the treetops, gliding is an energy-efficient strategy for making a quick getaway from potential predators or obtaining a tasty treat from the neighboring tree. It is perhaps unsurprising then that gliding has independently evolved in many different vertebrate groups.1 Most of these animals—like flying squirrels, sugar gliders, and Draco lizards—have developed large, wing-like folds of skin between their fore- and hindlimbs to create lift and prevent them from simply plummeting to the ground.

The paradise tree snake, of course, has no limbs to which such a membrane might be attached, and its noodle-shaped body does not seem ideal for generating lift or stability— yet somehow it is able to glide for several meters. This is exactly the kind of biophysical mystery that Jake Socha, an organismal biomechanics researcher at Virginia Tech, is drawn to solve. “I am very attracted to things that seem like they shouldn't work,” he said.

Socha’s work revealed that during gliding, the snake’s body shape transforms: normally vaguely circular in cross-section, the snake splays its ribs open, forming a triangle with a wide, slightly concave bottom. When Socha’s team analyzed the aerodynamic properties of this shape, they found that it generated surprisingly high amounts of lift when tilted at a 35-degree angle, identifying a mechanism that contributed to the snake’s gliding ability.2

Researchers also wondered how the reptile maintained stability in the air, executing a smooth glide rather than a tumbling fall. Taking advantage of a four-story black box performance space on campus, Socha’s team used high-speed motion capture to precisely measure the snake’s movements during the glide and develop a mathematical model. Using the model, they determined that the observed side-to-side undulation in the air—similar to the classic serpentine slither that snakes use to get around on land—boosted stability during gliding.3

Brightfield microscopy image of Aspergillus fumigatus.

The Silent Pandemic of Antifungal Resistance

As the world grapples with antimicrobial-resistant bacteria, another insidious threat looms large: drug-resistant fungi.

Image Credit:

Jos Houbraken

Photo of a blurred Ferry Hagen holding an agar plate with fungus up to the camera.
Ferry Hagen studies fungal pathogens to better understand drug resistance and develop new diagnostic tools.
Marjan Vermaas

Drug resistance in fungi like Candida auris and Aspergillus fumigatus leads to difficult-to-treat infections, earning them the distinction of ‘critical’ on the World Health Organization’s Fungal Priority Pathogen List.1 Drug-resistant bacteria often receive the largest share of research funding and attention, but experts warn of the growing threat of antifungal resistance. Ferry Hagen, a medical mycologist at the Westerdijk Fungal Biodiversity Institute, discussed the challenge in achieving recognition of the issue and developing therapeutics and diagnostic tools. 

Why do you refer to antifungal resistance as “the silent pandemic”?

While antibacterial resistance is widely acknowledged, antifungal resistance has not received the same attention.One reason is because fungal drug resistance spreads much slower than antibacterial resistance. For example, 20 years ago, antifungal-resistant A. fumigatus strains were rare, but now 15 percent of isolates in the Netherlands are resistant to one of the three classes of antifungals. Other species even exhibit resistance to two classes. 

What makes developing novel antifungals difficult?

Finding antifungal compounds that target fungi without harming patients is challenging due to the similarity between fungal and human cells. Additionally, developing new antifungals takes 10 to 15 years, but by then, many fungal strains have already developed resistance due to exposure to agricultural antimicrobials that target similar molecules.3 

Why are you interested in fungal genome sequencing?

Currently, medically-relevant fungal datasets are incomplete, largely because they were collected using the same genetic locus, but in some groups different loci can better identify fungal species. Additionally, the field lacks fungal diagnostic tools, limiting decision-making in the clinic and epidemiological studies. Increasing the coverage of fungal genome sequencing data could improve fungal detection and identification and lend insight into the genes orchestrating antifungal resistance.

This interview has been edited for length and clarity.

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A black snake encircled with pattens of red and yellow spots, curled up against a black background.

Science Crossword Puzzle

Put on your thinking cap, and take on this fun challenge.

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© istock.com, agus fitriyanto