“Being stuck at home was a blessing in disguise, as there were no experiments that could be done. We just had our computers and lots of time,” says Professor Paul Curmi, a structural biologist and molecular biophysicist with UNSW Sydney.

Prof. Curmi is referring to research published this month in Nature Communications that details the painstaking unravelling and reconstruction of a key protein in a single-celled, photosynthetic organism called a cryptophyte, a type of algae that evolved over a billion years ago.

Up until now, how cryptophytes acquired the proteins used to capture and funnel sunlight to be used by the cell had molecular biologists scratching their heads. They already knew that the protein was part of a sort of antenna that the organism used to convert sunlight into energy. They also knew that the cryptophyte had inherited some antenna components from its photosynthetic ancestors — red algae, and before that cyanobacteria, one of the earliest lifeforms on earth that are responsible for stromatolites.

But how the protein structures fit together in the cryptophyte’s own, novel antenna structure remained a mystery — until Prof. Curmi, PhD student Harry Rathbone and colleagues from University of Queensland and University of British Columbia pored over the electron microscope images of the antenna protein from a progenitor red algal organism made public by Chinese researchers in March 2020.

Unravelling the mystery meant the team could finally tell the story of how this protein had enabled these ancient single-celled organisms to thrive in the most inhospitable conditions — metres under water with very little direct sunlight to convert into energy.

Prof. Curmi says the major implications of the work are for evolutionary biology.

“We provide a direct link between two very different antenna systems and open the door for discovering exactly how one system evolved into a different system — where both appear to be very efficient in capturing light,” he says.

“Photosynthetic algae have many different antenna systems which have the property of being able to capture every available light photon and transferring it to a photosystem protein that converts the light energy to chemical energy.”

By working to understand the algal systems, the scientists hope to uncover the fundamental physical principles that underlie the exquisite photon efficiency of these photosynthetic systems. Prof. Curmi says these may one day have application in optical devices including solar energy systems.

EATING FOR TWO

To better appreciate the significance of the protein discovery, it helps to understand the very strange world of single-celled organisms which take the adage “you are what you eat” to a new level.

As study lead author, PhD student Harry Rathbone explains, when a single-celled organism swallows another, it can enter a relationship of endosymbiosis, where one organism lives inside the other and the two become inseparable.

“Often with algae, they’ll go and find some lunch — another alga — and they’ll decide not to digest it. They’ll keep it to do its bidding, essentially,” Mr Rathbone says. “And those new organisms can be swallowed by other organisms in the same way, sort of like a matryoshka doll.”

In fact, this is likely what happened when about one and a half billion years ago, a cyanobacterium was swallowed by another single-celled organism. The cyanobacteria already had a sophisticated antenna of proteins that trapped every photon of light. But instead of digesting the cyanobacterium, the host organism effectively stripped it for parts — retaining the antenna protein structure that the new organism — the red algae — used for energy.

And when another organism swallowed a red alga to become the first cryptophyte, it was a similar story. Except this time the antenna was brought to the other side of the membrane of the host organism and completely remoulded into new protein shapes that were equally as efficient at trapping sunlight photons.

EVOLUTION

As Prof. Curmi explains, these were the first tiny steps towards the evolution of modern plants and other photosynthetic organisms such as seaweeds.

“In going from cyanobacteria that are photosynthetic, to everything else on the planet that is photosynthetic, some ancient ancestor gobbled up a cyanobacteria which then became the cell’s chloroplast that converts sunlight into chemical energy.

“And the deal between the organisms is sort of like, I’ll keep you safe as long as you do photosynthesis and give me energy.”

One of the collaborators on this project, Dr Beverley Green, Professor Emerita with the University of British Columbia’s Department of Botany says Prof. Curmi was able to make the discovery by approaching the problem from a different angle.

“Paul’s novel approach was to search for ancestral proteins on the basis of shape rather than similarity in amino acid sequence,” she says.

“By searching the 3D structures of two red algal multi-protein complexes for segments of protein that folded in the same way as the cryptophyte protein, he was able to find the missing puzzle piece.”

PSC is a rare disease with a poor prognosis and can lead to cirrhosis of the liver or bile duct cancer. It affects 0.01% of the population but, even though it is rare, PSC is responsible for more than 10% of all liver transplants, making it the third most common indication on liver transplant waiting lists in Europe.

In the recent study, which has now been published in the leading journal Hepatology, the researchers were able to identify a molecular signature for ER stress both in the liver cells (hepatocytes) and also in the bile duct epithelium — and notably as a stand-alone factor that is independent of the disease stage or degree of liver fibrosis (laying down of scar tissue) as a precursor to possible liver cirrhosis. “Using transcriptional analysis, we were able to identify a personalised molecular signature of primary sclerosing cholangitis, which shows that patients with an impaired response to ER stress have a poorer prognosis with a higher incidence of complications,” explains Trauner. “This discovery also opens up new treatment options, since ER stress can be counteracted with drugs.”

Since the build-up of potentially toxic bile acids in cholestasis results in ER stress, it is now being attempted to restore this balance pharmacologically using the new bile acid therapeutics that are available. Beneficial effects can reportedly be expected from drugs already in clinically testing — however, more research has already been initiated to explore this further.

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Charles Hillman, a professor at Northeastern University in Boston and co-author of this study, has suggested in previous research that there is a link between children’s cardiorespiratory fitness and their academic performance, as well as a beneficial effect of cardiorespiratory fitness on executive functions. “There are three main executive functions,” explains Marc Yangüez, a researcher at the UNIGE’s Faculty of Psychology and Educational Sciences (FPSE) and first author of the study. “The first is inhibition, i.e., our ability to inhibit intrusive or irrelevant behaviour or thoughts. The second is cognitive flexibility, which often called multitasking, and refers to our ability to flexibility move between tasks or responses based on task demands. Finally, the third is working memory, which is our ability to maintain information in our minds and manipulate it.”

However, the link between fitness and academic skills does not seem obvious at first sight. This is why researchers at the UNIGE wanted to analyze it and observe how one influences the other and whether a specific cognitive process plays a predominant role.

Testing the physical and cognitive abilities of Geneva students

The Geneva investigators teamed up with eight schools in the canton of Geneva to conduct cognitive and physical tests on 193 pupils aged 8 to 12. First of all, children took a physical test known as the “shuttle run test”: the children had to run back and forth between two lines 20 meters apart at an increasingly fast pace. “Combined with height, weight, age and sex, this test allows us to assess the child’s cardiovascular fitness,” says Marc Yangüez. “Following this, we used nine tasks that allow us to assess children’s abilities in the three main executive functions — inhibition, cognitive flexibility and working memory — and we measured different indicators such as the precision and speed of their responses,” explains Julien Chanal, researcher at the FPSE of the UNIGE. For example, one of the tests of inhibition presents students with images of fish swimming. The central fish can either swim in the same direction as the others or in the opposite direction. The students have to indicate as quickly and accurately as possible the direction in which the central fish is swimming when they are only shown the picture for 200 milliseconds. To measure cognitive flexibility, the students took three tests as well, one of the tests asked the students to connect in ascending order numbers and letters (1-A-2-B-3-C, etc.). In one of the working memory tests, the students had to memorize a sequence of numbers, such as 2 6 4 9 7, and then repeat them in the reverse order. In addition, at the end of the year, the teachers, with the parents’ consent, transmitted the students’ marks for the three terms of the year in mathematics, French 1 (comprehension and expression of text) and French 2 (grammar, spelling and vocabulary).

An indirect link between cardiorespiratory fitness and school results

By combining the data obtained, the psychologists found that there was a link between better cardiorespiratory fitness and higher marks in mathematics and French 2. “French 1 is probably less directly concerned, because the evaluation of the text and the writing depend more on subjective factors, which is less the case for mathematics or grammar, for which there is little subjectivity in the right or wrong answers,” explains Marc Yangüez. In addition to the existence of a link between cardiorespiratory fitness and school results, the data obtained also confirm a link between cardiorespiratory fitness and executive functions. But does good cardiorespiratory fitness affect academic performance directly or indirectly through executive functions?

“By decomposing these effects via a statistical mediation model, we established that the link between cardiorespiratory fitness and academic performance was indirect. In fact, physical fitness is related to better executive functions, and it is indeed executive functions that influences school performance, more specifically cognitive flexibility,” emphasizes Julien Chanal.

Important results for the planning of physical education in schools

The results of this study are important for the organization of school planning. “By demonstrating the link between physical capacities, such as cardiorespiratory capacity, cognitive abilities and grades, it underlines the importance of not reducing physical activity (and in particular physical education hours) in favour of other subjects, as this could ultimately have a negative impact on the development of the child as a whole,” says Marc Yangüez. This study also challenges the idea of forcing children to study more and spend more time at their desks in order to succeed at school, depriving them of physical exercise. Finally, and all the more so in times of a pandemic, the Geneva psychologists stress the importance of not depriving children of movement, which would be detrimental to both their physical health and their cognitive health. “We would now like to carry out an intervention study into schools in different regions of Switzerland, in order to demonstrate on a large scale that when children’s weekly physical activity increases, it has a positive impact on the development of executive functions, leading to a significant improvement in school results,” concludes Julien Chanal.

The research findings have been published in the academic journal Molecular Biology and Evolution.

Due to the general lack of photosynthesis-derived organic matter, the deep-sea was once considered a vast “desert” with very little biomass. Yet, clams often form large populations in the high-temperature hydrothermal vents and freezing cold seeps in the deep oceans around the globe where sunlight cannot penetrate but toxic molecules, such as hydrogen sulfide, are available below the seabed. The clams are known to have a reduced gut and digestive system, and they rely on endosymbiotic bacteria to generate energy in a process called chemosynthesis. However, when this symbiotic relationship developed, and how the clams and chemoautotrophic bacteria interact, remain largely unclear.

Horizontal gene transfer between bacteria and clams discovered for the first time

A research team led by Professor Qiu Jianwen, Associate Head and Professor of the Department of Biology at HKBU, collected the clam specimens at 1,360 metres below sea level from a cold seep in the South China Sea. The genomes of the clam and its symbiotic bacteria were then sequenced to shed light on the genomic signatures of their successful symbiotic relationship.

The team found that the ancestor of the clam split with its shallow-water relatives 128 million years ago when dinosaurs roamed the earth. The study revealed that 28 genes have been transferred from the ancestral chemoautotrophic bacteria to the clam, the first discovery of horizontal gene transfer — a process that transmits genetic material between distantly-related organisms — from bacteria to a bivalve mollusc.

The following genomic features of the clam were discovered, and combined, they have enabled it to adapt to the extreme deep-sea environment:

(1) Adaptions for chemosynthesis

The clam relies on its symbiotic chemoautotrophic bacteria to produce the biological materials essential for its survival. In their symbiotic relationship, the clam absorbs hydrogen sulfide from the sediment, and oxygen and carbon dioxide from seawater, and it transfers them to the bacteria living in its gill epithelium cells to produce the energy and nutrients in a process called chemosynthesis. The process is illustrated in Figure 1.

The research team also discovered that the clam’s genome exhibits gene family expansion in cellular processes such as respiration and diffusion that likely facilitate chemoautotrophy, including gas delivery to support energy and carbon production, the transfer of small molecules and proteins within the symbiont, and the regulation of the endosymbiont population. It helps the host to obtain sufficient nutrients from the symbiotic bacteria.

(2) Shift from phytoplankton-based food

Cellulase is an enzyme that facilitates the decomposition of the cellulose found in phytoplankton, a major primary food source in the marine food chain. It was discovered that the clam’s cellulase genes have undergone significant contraction, which is likely an adaptation to the shift from phytoplankton-derived to bacteria-based food.

(3) Adaptation to sulfur metabolic pathways

The genome of the symbiont also holds the secrets of this mutually beneficial relationship. The team discovered that the clam has a reduced genome, as it is only about 40% of the size of its free-living relatives. Nevertheless, the symbiont genome encodes complete and flexible sulfur metabolic pathways, and it retains the ability to synthesise 20 common amino acids and other essential nutrients, highlighting the importance of the symbiont in generating energy and providing nutrients to support the symbiotic relationship.

(4) Improvement in oxygen-binding capacity

Unlike in vertebrates, haemoglobin, a metalloprotein found in the blood and tissues of many organisms, is not commonly used as an oxygen carrier in molluscs. However, the team discovered several kinds of highly expressed haemoglobin genes in the clam, suggesting an improvement in its oxygen-binding capacity, which can enhance the ability of the clam to survive in deep-sea low-oxygen habitats.

Professor Qiu said: “Most of the previous studies on deep-sea symbiosis have focused only on the bacteria. This first coupled clam-symbiont genome assembly will facilitate comparative studies that aim to elucidate the diversity and evolutionary mechanisms of symbiosis, which allows many invertebrates to thrive in ‘extreme’ deep-sea ecosystems.”

The research was jointly conducted by scientists from HKBU and the HKBU Institute for Research and Continuing Education, the Hong Kong Branch of the Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), The Hong Kong University of Science and Technology, City University of Hong Kong, the Japan Agency for Marine-Earth Science and Technology, the Sanya Institute of Deep-Sea Science and Engineering, and the Guangzhou Marine Geological Survey.