A “Nano-Robot” Built Entirely from DNA to Explore Cell Processes

Scientists have designed a “nano-robot” made up of three DNA origami structures. © Gaëtan Bellot/Inserm

Constructing a tiny robot from DNA and using it to study cell processes invisible to the naked eye… You would be forgiven for thinking it is science fiction, but it is in fact the subject of serious research by scientists from Inserm, CNRS and Université de Montpellier at the Structural Biology Center in Montpellier[1]. This highly innovative “nano-robot” should enable closer study of the mechanical forces applied at microscopic levels, which are crucial for many biological and pathological processes. It is described in a new study published in Nature Communications.

Our cells are subject to mechanical forces exerted on a microscopic scale, triggering biological signals essential to many cell processes involved in the normal functioning of our body or in the development of diseases.

For example, the feeling of touch is partly conditional on the application of mechanical forces on specific cell receptors (the discovery of which was this year rewarded by the Nobel Prize in Physiology or Medicine).

In addition to touch, these receptors that are sensitive to mechanical forces (known as mechanoreceptors) enable the regulation of other key biological processes such as blood vessel constriction, pain perception, breathing or even the detection of sound waves in the ear, etc.

The dysfunction of this cellular mechanosensitivity is involved in many diseases – for example, cancer: cancer cells migrate within the body by sounding and constantly adapting to the mechanical properties of their microenvironment. Such adaptation is only possible because specific forces are detected by mechanoreceptors that transmit the information to the cell cytoskeleton.

At present, our knowledge of these molecular mechanisms involved in cell mechanosensitivity is still very limited. Several technologies are already available to apply controlled forces and study these mechanisms, but they have a number of limitations. In particular, they are very costly and do not allow us to study several cell receptors at a time, which makes their use very time-consuming if we want to collect a lot of data.

DNA origami structures

In order to propose an alternative, the research team led by Inserm researcher Gaëtan Bellot at the Structural Biology Center (Inserm/CNRS/Université de Montpellier) decided to use the DNA origami method. This enables the self-assembly of 3D nanostructures in a pre-defined form using the DNA molecule as construction material. Over the last ten years, the technique has allowed major advances in the field of nanotechnology.

This enabled the researchers to design a “nano-robot” composed of three DNA origami structures. Of nanometric size, it is therefore compatible with the size of a human cell. It makes it possible for the first time to apply and control a force with a resolution of 1 piconewton, namely one trillionth of a Newton – with 1 Newton corresponding to the force of a finger clicking on a pen. This is the first time that a human-made, self-assembled DNA-based object can apply force with this accuracy.


The team began by coupling the robot with a molecule that recognizes a mechanoreceptor. This made it possible to direct the robot to some of our cells and specifically apply forces to targeted mechanoreceptors localized on the surface of the cells in order to activate them.

Such a tool is very valuable for basic research, as it could be used to better understand the molecular mechanisms involved in cell mechanosensitivity and discover new cell receptors sensitive to mechanical forces. Thanks to the robot, the scientists will also be able to study more precisely at what moment, when applying force, key signaling pathways for many biological and pathological processes are activated at cell level.

“The design of a robot enabling the in vitro and in vivo application of piconewton forces meets a growing demand in the scientific community and represents a major technological advance. However, the biocompatibility of the robot can be considered both an advantage for in vivo applications but may also represent a weakness with sensitivity to enzymes that can degrade DNA. So our next step will be to study how we can modify the surface of the robot so that it is less sensitive to the action of enzymes. We will also try to find other modes of activation of our robot using, for example, a magnetic field,” emphasizes Bellot.


[1] Also contributed to this research: the Institute of Functional Genomics (CNRS/Inserm/Université de Montpellier), the Max Mousseron Biomolecules Institute (CNRS/Université de Montpellier/ENSCM), the Paul Pascal Research Center (CNRS/Université de Bordeaux) and the Physiology and Experimental Medicine: Heart-Muscles laboratory (CNRS/Inserm/Université de Montpellier).

Questioning the Universal Application of Neurocognitive Tests


Human interactions are enabled by a set of neurocognitive mechanisms defined by the concept of “social cognition”. © Ryoji Iwata /Unsplash

Human interactions are enabled by a set of neurocognitive mechanisms defined by the concept of “social cognition”. In order to identify social cognition disorders, specialists use internationally validated evaluation tests. However, these are most often developed in western, industrialized countries, which could question the relevance of applying them to all humanity. A research team from Inserm, University Hospital Lille, and Université de Lille within the Lille Neuroscience & Cognition laboratory looked at the impact of cultural differences on the performances on two of the neurocognitive tests most used worldwide, comparing the results of around 600 healthy participants across 12 countries. Their study, to be published in Neuropsychology, highlights notable differences in performance from one country to another and calls for more consideration to be given to the social sciences when developing such tests.

The concept of “social cognition” designates the various cognitive processes (perception, memorization, reasoning, emotion…) involved in social interactions. Disorders of social cognition are encountered in many diseases, such as schizophrenia and Parkinson’s, and in neurodevelopmental disorders, such as autism. They are responsible for highly incapacitating interpersonal difficulties that strongly impact the lives of patients and those around them. Consequently, the detection, quality of evaluation, and treatment of such disorders represent a major challenge for mental health specialists.

To evaluate social cognition capacities and diagnose a potential disorder, there are tests used internationally that measure “cognitive functions” – namely the capacities that enable us to interact effectively with others.

However, these reference cognitive tests are most often developed in western, industrialized, and democratic countries and their “norms” for the most part based on profiles of well-educated, rich, white people. Insofar as such individuals constitute only 12 % of humanity, their overrepresentation in the development of neuropsychological tests calls into question the relevance of their application to other populations.

A team of scientists led by Inserm researcher Maxime Bertoux within the Lille Neuroscience & Cognition laboratory (Inserm/University Hospital Lille/Université de Lille) sought to determine whether cultural differences have a notable impact on the results of the most commonly used social cognition tests. This involved conducting a vast international study on 587 healthy participants, from 18 to 89 years of age, across 12 countries (Germany, England, Argentina, Brazil, Canada, Chili, China, Colombia, Spain, France, Italy, and Russia). Neuropsychologists subjected the participants to two types of test evaluating the capacities considered essential in social cognition.

The first, devised in the UK, evaluated the capacity to decode social rules and infer others’ mental state by asking the participants to identify, in various short scenes, whether one of the characters was committing a social faux pas (for example, mistaking a customer for a waiter in a restaurant). The second test, devised in the US, evaluated the capacity to recognize the expression of emotions by asking the participants to identify various facial expressions on photographs.

The results of the study show that a large proportion of the divergences in performance on these two tests (around one quarter for the faux pas test and over 20 % for the emotions recognition test) is attributable to the differences in nationality of the participants.

The best performances in the faux pas test were obtained by the English participants, without the literal translation from English to the other participants’ native languages having an impact on the results.

For example, 100 % of the English participants considered it a faux pas to mistake a customer for a waiter in a restaurant versus only 65 % of the Canadian participants. Furthermore, while 100 % of the English participants considered it normal to give up their seat on a bus for an elderly person, 21 % of the Chinese participants considered it a faux pas.

In the results of the emotional facial expression recognition test, the comparison between the countries reveals that some emotions were not identified in the same way by all participants. While positive expressions such as joy were interpreted unambiguously from one country to another, the interpretation of negative emotions was much more variable. For example, fear was confused with surprise by the majority of the Canadian and Brazilian participants, whereas the English and Argentinians had virtually no difficulty differentiating them.

This study shows that individual and cultural factors have a strong impact on social cognition measures, declares Bertoux. Beyond the effect of age, gender, and education, there is an influence of local concepts, norms and habits on the categorization of emotions, inferring others’ intentions and understanding their behavior. As such, the use of tests devised by rich, white US or UK scientists, would favor the performance of the participants from the same country, culture, and social level.

Of course, this does not mean that the inhabitants of one country are superior or inferior to those of another, adds the researcher. Our study shows that a test devised in a specific context favors those who are familiar with that context. For example, identifying a faux pas requires detecting that an implicit social rule has been broken – but social rules fluctuate from one country to another.” 

These findings therefore question the international applicability of a neuropsychological test devised and validated in one country, particularly when it comes to evaluating and diagnosing cognitive disorders. 

For its future studies, the research team would like to enrich its data by including more participants and countries – particularly regions of the world not represented in this research, such as Africa and the Middle East –, but also by exploring the neurocognitive and cultural variations within vast countries such as China and Canada. “The neurosciences need to interact more with the social sciences in exploring and considering cultural diversity in order to build a more rigorous, relevant, and inclusive neuropsychology,” concludes Bertoux.

Inserm and CNRS to Lead Large-Scale Program on Psychiatry Research


Psychiatric illnesses constitute a major public health problem. © Danie Franco/Unsplash

On July 18, 2022, France’s minister for Higher Education and Research Sylvie Retailleau announced an unprecedented psychiatry research effort in the form of 80 million euros allocated over five years to the precision-psychiatry project-program PROPSY, led by Inserm and CNRS as part of the Priority Research and Resources Programs (PEPRs). With this ambitious research program centered around four of the most incapacitating psychiatric disorders, the two institutes aim to develop precision psychiatry in order to revolutionize both their diagnosis and patient care.

Led jointly by Inserm and CNRS, the project will involve partners whose competences are both renowned and complementary, such as Fondation FondaMental, CEA, Sorbonne Université, Université de Bordeaux, Université de Lille, Université de Paris, and Université Paris Est Créteil.

Psychiatric illnesses constitute a major public health problem, affecting 20 % of French people on a daily basis – and very often their loved ones. Developing early in life, these illnesses often strike young adults and are sadly linked to a 10-to-20-year reduction in life expectancy. In response to the diagnoses – that are sometimes long in coming – the therapeutic options are often thin on the ground, with those that are available having incapacitating side effects. Not to mention the considerable socioeconomic impact, with recent estimations putting the direct and indirect costs at 160 billion euros in 2019 – representing over 5 % of GDP.

Faced with these two observations, it would appear imperative to improve the coordination of France’s psychiatry research forces and increase the research-care continuum. These are the proposals of PROPSY, a project led by Inserm and CNRS which has recently been selected to receive 80-million-euro funding over five years.

Centered around four of the most incapacitating disorders, bipolar disorder, major depressive disorders, schizophrenia, and autism spectrum disorders, this exploratory PEPR will broaden the field of precision medicine in psychiatry.

This will make it possible to provide each patient with the best care. In order to achieve this ambition, the multiple challenges will be to:

  • Better understand the causes and mechanisms behind mental illnesses
  • Discover prognostic markers for these disorders and identify homogenous patient subgroups
  • Develop targeted therapeutic strategies that include eHealth, immunomodulators, brain stimulation, and biotherapies
  • Reduce stigma and false representations
  • Support the development of a French biomedical sector in mental health, including pharma, MedTech and digital, through public-private partnerships
  • Create a new generation of scientists and medical staff in psychiatry by renewing the approach to these illnesses and thanks to training initiatives

Selected as part of the call for Priority Research and Resources Programs, PROPSY will include the funding of projects already identified – such as the French Minds longitudinal cohort of 3 000 adult patients who will undergo exhaustive clinical, behavioral, and environmental evaluation with the help of digital tools, biological markers, and brain imaging – as well as open calls for proposals.

We are proud that the government has selected our research program,” confide Gilles Bloch, Inserm CEO and Marion Leboyer, 2021 Inserm Grand Prize recipient, Executive Director of the FondaMental foundation and project scientific lead. “With the negative impact of the health crisis on mental health (an over 30 % increase in cases of depression), this extremely important decision represents hope for millions of patients, their families, as well as researchers and medical staff. “


With the benefit of better support for patients, the PROPSY PEPR will enable research and patient care to join forces to meet the public health challenges related to psychiatric disorders,” adds Antoine Petit, Chairman and CEO of CNRS.

Towards a New Drug Class in the Treatment of Type 2 Diabetes

Mouse visceral adipose tissue fluorescently labeled with AdipoRed. Nuclei are stained blue. © Vincent Marion.

Type 2 diabetes is a major public health problem that affects millions of people worldwide. Developing new drugs to help better treat its underlying causes is therefore a research priority. In a new study coordinated by Inserm researcher Vincent Marion in collaboration with the University of Birmingham (UK), Monash University (Australia), and along with Alexander Fleming, former senior endocrinologist at the US Food and Drug Administration (FDA), the scientists have developed PATAS, a peptide that is part of a new class of antidiabetic drugs. PATAS can correct the metabolic abnormalities leading to type 2 diabetes and its associated comorbidities which include insulin resistance[1]. PATAS works by specifically targeting the adipocytes (fat cells)[2], restoring glucose entry and thus correcting and re-establishing the metabolic physiology of the adipose tissue. The teams hope to set up a clinical trial soon to test this new therapy. Their study has been published in the journal Diabetes.

Diabetes mellitus is a chronic condition that affects 537 million people worldwide, with the majority affected by type 2 diabetes. The prevalence of type 2 diabetes, which is characterized by high levels of glucose in the blood (see box), has been increasing for decades due to population aging, inactivity, and poor diet. The age of onset is also decreasing, and although the disease is considered to be an “adult disease”, it is now seen frequently in adolescents and children.

Available drugs treat the consequences of type 2 diabetes by focusing mainly on lowering blood glucose; they do not target the underlying biological mechanism that causes the disease.

Despite the urgency for developing new and more effective treatments, there have been no disruptive therapeutic innovations to reach market in over a decade.

And this is precisely the objective of the research led by Inserm researcher Vincent Marion and his team at the Medical Genetics Laboratory (Inserm/Université de Strasbourg). In a recent study in collaboration with the University of Birmingham and Monash University, the scientists have developed a product called PATAS in a new class of diabetes drugs called “Adipeutics” (for therapies that specifically target the adipocytes).

Their study, conducted on animal models, shows that this new therapy specifically restores glucose uptake in the adipocytes, resulting in the treatment of insulin resistance with beneficial effects on the whole body. This is made all the more promising by the fact that treating insulin resistance has the potential to address not only type 2 diabetes but a large array of serious medical conditions that result from this resistance.

Type 2 diabetes in brief

Diabetes mellitus is characterized by excessive blood glucose levels over a prolonged period of time: this is known as hyperglycemia.

Hyperglycemia is caused by a reduced sensitivity of the cells, particularly those in the liver, muscle, and adipose tissue, to insulin. This is known as “insulin resistance.”

Insulin is a hormone produced by the pancreas whose role is to facilitate the entry of glucose into the body cells as their main source of energy. To meet the increased demand for insulin caused by the cells’ resistance to this hormone, the pancreas produces even more insulin, depleting the body requirements. Insulin production then becomes insufficient and the blood glucose levels rise as a result.

The role of adipocytes

This study follows on from years of rigorous, in depth work carried out in the lab. In previous research, published in Diabetes in 2020, the scientists had identified a new therapeutic target for type 2 diabetes when investigating at an ultra-rare monogenic disease known as Alström syndrome.

The scientists had shown that adipose tissue abnormalities caused by a dysfunctional protein called ALMS1 led to extremely severe insulin resistance associated with early-onset type 2 diabetes in people with Alström syndrome. In animal models, restoring the function of this protein within the adipocytes re-established blood glucose balance.

The teams then went on to focus more closely on ALMS1 and how it interacts with other proteins within the adipocytes. In particular, they have shown that in the absence of insulin, ALMS1 binds to another protein called PKC alpha. The activation of insulin in the adipocytes induces the separation of these two proteins ALMS1 and PKC alpha, resulting in glucose entry into cells. In people with diabetes, who are insulin-resistant, this link between the two proteins is maintained.

Drawing on this knowledge, the scientists have developed the peptide PATAS, which works by breaking the interaction between ALMS1 and PKC alpha – thus restoring insulin signaling in the adipocytes.

In mouse models of diabetes, PATAS has been able to re-establish the normal physiology of the adipocytes by restoring glucose uptake. “Thanks to PATAS, the adipocytes that could no longer access glucose were once again able to absorb it and then metabolize it in order to synthesize and secrete lipids which are beneficial to the entire body. These positive effects are visible in our animal models, with a marked improvement in insulin resistance. Other parameters and comorbidities are also improved, including better blood glucose control and decreased liver fibrosis and steatosis,” explains Vincent Marion.

These promising results in animals have paved the way for the researchers to organize a clinical trial as soon as possible, in order to test PATAS in humans. The successful development of a new class of antidiabetic drugs could have significant implications for public health, not only to treat type 2 diabetes but also many other cardio-metabolic disorders in which dysfunctional adipocytes and insulin resistance are very problematic.

In order to create value from these findings and facilitate the organization of such a trial, Vincent Marion has founded the start-up AdipoPharma SAS.


[1] Insulin resistance is when cells in your muscles, fat, and liver do not respond well to the hormone insulin and can’t use glucose from the blood as their energy source. Insulin resistance is the basis of high blood fats, heart and vascular disorders, metabolic syndrome and type 2 diabetes

[2] Adipose tissue is a set of cells known as adipocytes that store fats.

Scientists discover novel mutation associated with alternating hemiplegia of childhood

hémiplégie alternante de l'enfant (HAE)

The effect of G60R mutation on CLDN-5 expression and localization in CLDN-null cells. © Matthew Campbell, Smurfit Institute of Genetics, Trinity College Dublin

Scientists at Trinity College Dublin and the Institute Imagine at Necker Hospital, Paris, announced a significant advance in our understanding of a very rare condition called alternating hemiplegia of childhood (AHC). This is a devastating condition that can lead to repeated paralysis that affects one side of the body or the other or sometimes both at once. It usually begins to affect children before 18 months of age and to date, only one causative gene has been identified.

Here, scientists in Dublin and Paris have now identified a second gene CLDN5 as being responsible for the condition in 2 unrelated cases of AHC in France. The protein product of this gene, claudin-5, is critical for maintaining the integrity of the blood-brain barrier (BBB). Intriguingly, the mutated form of the protein turns the barrier into a channel that is selective for negatively charged ions. In this regard, the ionic compositions of the brain are likely shifted in these children and this is a key driver of the condition.

“This finding was based on an amazing collaboration with Prof Arnold Munnich’s group at the Institute Imagine in Paris. The identity of these de novo mutations in unrelated children suggests that the barrier is turning into a channel. This is exciting on numerous levels as it is the first report of the BBB turning into a channel, but it also sheds light on the devastating pathology of AHC which may assist in clinical management of patients with this mutation” said Dr Matthew Campbell, Associate Professor at Trinity.

Importantly, the work has implications for our basic understanding of the junctional protein that forms the BBB. As this is the first report of the human BBB becoming a channel, there may be avenues for drug delivery that have never been explored. This will now form the basis of the next steps of the project.

Dr Yosuke Hashimoto, visiting researcher from the Japanese Society for the Promotion of Science (JSPS), and his equally contributing colleague Dr Karine Poirier from the Institute Imagine added: “This exciting project has shed light on a very rare condition affecting children. We are delighted that our work was able to quickly identify the causative mutation for the disease as well as progressing our understanding of the pathology of the disease.”

Commenting on the study, Prof Arnold Munnich from the Institute Imagine in Paris said “We are delighted this work has progressed so quickly and our groups have been able to work very closely to identify the cause of this condition. Studies like this will benefit families and clinicians immensely in the years to come”.

A multidisciplinary team of Geneticists, Neurologists and Radiologists from Ireland and France undertook the study.

The research, published this week in the international journal, Brain was supported by Science Foundation Ireland (SFI), FutureNeuro, Japanese Society for the Promotion of Science (JSPS) and the European Research Council (ERC)