An unprecedented view of gene regulation

Caption:“Using this method, we generate the highest-resolution maps of the 3D genome that have ever been generated, and what we see are a lot of interactions between enhancers and promoters that haven't been seen previously,” says Anders Sejr Hansen, the Underwood-Prescott Career Development Assistant Professor of Biological Engineering at MIT. 

Video Credit: Melanie Gonick/MIT

Much of the human genome is made of regulatory regions that control which genes are expressed at a given time within a cell. Those regulatory elements can be located near a target gene or up to 2 million base pairs away from the target.

To enable those interactions, the genome loops itself in a 3D structure that brings distant regions close together. Using a new technique, MIT researchers have shown that they can map these interactions with 100 times higher resolution than has previously been possible.

“Using this method, we generate the highest-resolution maps of the 3D genome that have ever been generated, and what we see are a lot of interactions between enhancers and promoters that haven't been seen previously,” says Anders Sejr Hansen, the Underwood-Prescott Career Development Assistant Professor of Biological Engineering at MIT and the senior author of the study. “We are excited to be able to reveal a new layer of 3D structure with our high resolution.”

The researchers’ findings suggest that many genes interact with dozens of different regulatory elements, although further study is needed to determine which of those interactions are the most important to the regulation of a given gene.

T Cells Can Activate Themselves to Fight Tumors

T cells are a type of white blood cell and play a central role in the immune response.
Photo Credit: NIAID.

When you need a bit of motivation, it often has to come from within. New research suggests cancer-fighting immune cells have found a way to do just that.

Scientists at University of California San Diego have discovered a property of T cells that could inspire new anti-tumor therapeutics. Through a previously undescribed form of cell auto-signaling, T cells were shown to activate themselves in peripheral tissues, fueling their ability to attack tumors.

The study, published May 8, 2023 in Immunity, was led by study first author and postdoctoral fellow Yunlong Zhao, PhD, and co-senior authors Enfu Hui, PhD, professor in the School of Biological Sciences at UC San Diego and Jack D. Bui, MD, PhD, professor of pathology at UC San Diego School of Medicine.

T cells are a type of white blood cell that protect against infection and help fight cancer. In the lymph organs, T cells are trained by antigen-presenting cells, which, as their name suggests, present an antigen (a piece of tumor or pathogen) to T cells, stimulating an immune response. 

A new at­las il­lus­trates how the hu­man ret­ina is de­vel­op­ing.

De­tail of a cross-​section of a ret­inal or­ganoid. Dif­fer­ent tis­sue struc­tures are made vis­ible with dif­fer­ent colors.
Pho­to­ Credit: Wahle et al. Nature Bi­o­tech­no­logy 2023

What cell types are found in which hu­man tis­sue, and where? Which genes are act­ive in the in­di­vidual cells, and which pro­teins are found there? An­swers to these ques­tions and more are to be provided by a specialized at­las – in par­tic­u­lar how the dif­fer­ent tis­sues form dur­ing em­bryonic de­vel­op­ment and what causes dis­eases. In cre­at­ing this at­las, re­search­ers aim to map not only tis­sue dir­ectly isol­ated from hu­mans, but also struc­tures called or­ganoids. These are three-​dimensional clumps of tis­sue that are cul­tiv­ated in the labor­at­ory and de­velop in a way sim­ilar to hu­man or­gans, but on a small scale.

“The ad­vant­age of or­ganoids is that we can in­ter­vene in their de­vel­op­ment and test act­ive sub­stances on them, which al­lows us to learn more about healthy tis­sue as well as dis­eases,” ex­plains Bar­bara Treut­lein, Pro­fessor of Quant­it­at­ive De­vel­op­mental Bio­logy at the De­part­ment of Biosys­tems Sci­ence and En­gin­eer­ing at ETH Zurich in Basel.

To help pro­duce such an at­las, Treut­lein, to­gether with re­search­ers from the Uni­ver­sit­ies of Zurich and Basel, has now de­veloped an ap­proach to gather and com­pile a great deal of in­form­a­tion about or­ganoids and their de­vel­op­ment. The re­search team ap­plied this ap­proach to the or­ganoids of the hu­man ret­ina, which they de­rived from stem cells.

Researchers develop model for how the brain acquires essential omega-3 fatty acids

Step-by-step process of lipid transport across blood-brain barrier.
Illustration Credit: Ethan Tyler from NIH Medical Arts

Researchers at the UCLA David Geffen School of Medicine, the Howard Hughes Medical Institute at UCLA and the National Institutes of Health have developed a zebrafish model that provides new insight into how the brain acquires essential omega-3 fatty acids, including docosahexaenoic acid (DHA) and linolenic acid (ALA). Their findings, published in Nature Communications, have the potential to improve understanding of lipid transport across the blood-brain barrier and of disruptions in this process that can lead to birth defects or neurological conditions. The model may also enable researchers to design drug molecules that are capable of directly reaching the brain.

Omega-3 fatty acids are considered essential because the body cannot make them and must obtain them through foods, such as fish, nuts and seeds. DHA levels are especially high in the brain and important for a healthy nervous system. Infants obtain DHA from breastmilk or formula, and deficiencies of this fatty acid have been linked to problems with learning and memory. To get to the brain, omega-3 fatty acids must pass through the blood-brain barrier via the lipid transporter Mfsd2a, which is essential for normal brain development. Despite its importance, scientists did not know precisely how Mfsd2a transports DHA and other omega-3 fatty acids.

X-ray beams help researchers learn new tricks from old metals

 

An intense X-ray beam (in pink) is focused into a small spot on a single nanoscale grain of a platinum electrode (highlighted within the droplet). Diffraction interference patterns from that grain were collected on an X-ray detector (the black screen).
Illustration Credit: Dina Sheyfer, Argonne National Laboratory.

A research team led by the U.S. Department of Energy’s (DOE) Argonne National Laboratory used powerful X-ray beams to unlock a new understanding of materials important to the production and use of hydrogen. The goal is to make hydrogen production and usage more efficient and less expensive, offering a better fuel for transportation and industry.

“Efficient hydrogen production is key,” said Hoydoo You, an Argonne senior physicist. ​“Hydrogen is the lightest energy storage material. Hydrogen can be produced from water using renewable energy or excess energy, transported as a fuel, and converted back to water to produce energy for consumers. Platinum and its alloys are best in catalyzing and boosting the water-splitting process by accelerating the exchange of electrons.”

Understanding and developing materials enabling efficient production and usage of hydrogen are key to the hydrogen economy. The researchers made a first step in developing a tool that enables them to characterize the materials with a new level of detail, ultimately producing the best materials for hydrogen production and use.

Study sheds light on how the immune system protects the body

Photo Credit: RDNE Stock project

Researchers explore how patients with a rare and severe immunodeficiency were still able to defend themselves normally against viruses, including COVID-19

The first study of humans with a rare immunodeficiency reveals how the immune system protects the body against pathogens known to cause serious diseases, such as tuberculosis and COVID-19. The research involving McGill University, paves the way for new therapies to treat autoimmune diseases, chronic inflammatory diseases, and new approaches to vaccine development.

The immune system responds differently to various types of pathogens, like bacteria, parasites, and viruses. However, scientists are still trying to uncover how this complex network functions together and the processes that can go wrong with immunodeficiencies.

“The immune system plays a vital role in protecting the body from harmful germs that make people ill. It’s made up of a complex network of organs, cells, and proteins – like IRF1 or regulatory factor 1, which is key in the regulation of an early immune response to pathogens,” says co-author of the study David Langlais, an Assistant Professor in the Departments of Human Genetics and Microbiology and Immunology at McGill University.

Prolonging the survival of patients with gastric cancer

Zolbetuximab is given as an intravenous infusion to patients with advanced gastric cancer in combination with chemotherapy.
Photo Credit: Hiroshi Tsubono

Gastric cancer is the fifth most commonly diagnosed malignancy worldwide. It ranks a sad third in cancer-related causes of death. The reason for this is late diagnosis coupled with rapid spread of tumor cells in the body. In an international clinical study co-chaired by investigators from Leipzig University’s Faculty of Medicine, researchers investigated a substance that is expected to prolong the survival of patients and also established a new clinically relevant biomarker. The results have been published in the renowned journal “The Lancet”.

“The results of the study are important for cancer research. They show that patients with gastric cancer who have been treated with zolbetuximab live longer. The progression of the tumor disease is delayed and overall survival of patients is improved. We expect that the study will lead to the approval of this drug in Europe and as a result also in Germany. This is an important step for those affected by this serious and often fatal cancer,” said Professor Florian Lordick, director of the University Cancer Center Leipzig. The experienced oncologist helped to design the recently published study at the international level and ensured that German patients were able to participate.

Efficient synthesis of indole derivatives, an important component of most drugs, allows the development of new drug candidates

Efficient synthesis of indole derivatives, an important component of most drugs,  allows the development of new drug candidates. 
Illustration Credit: Reiko Matsushita

A research group at Nagoya University in Japan has successfully developed an ultrafast and simple synthetic method for producing indole derivatives. Their findings are expected to make drug production more efficient and increase the range of potential indole-based pharmaceuticals to treat a variety of diseases. Their findings were published in Communications Chemistry. 

An indole is an organic compound consisting of a benzene ring and a pyrrole ring. Heteroatom alkylation at the carbon atom next to the indole ring is particularly useful to create a wide range of new indole derivatives and many anti-inflammatory, anticancer, and antimicrobial treatments contain them.

In the past, this heteroatom alkylation has proven difficult because indoles easily and rapidly undergo unwanted dimerization/multimerization, processes in which two or more molecules combine during the reaction to form unwanted larger molecules. These unwanted by-products limit the yield of the desired product.  

The evolution of honey bee brains

European honey bee worker. The researchers studied honey bees exhibiting different behaviors: foragers, nurse bees, and queens. Honey bees in general have been a key insect model for better understanding learning and memory for more than 100 years.
Photo Credit: ©2023 Hiroki Kohno

Researchers have proposed a new model for the evolution of higher brain functions and behaviors in the Hymenoptera order of insects. The team compared the Kenyon cells, a type of neuronal cell, in the mushroom bodies (a part of the insect brain involved in learning, memory and sensory integration) of “primitive” sawflies and sophisticated honey bees. They found that three diverse, specialized Kenyon cell subtypes in honey bee brains appear to have evolved from a single, multifunctional Kenyon cell-subtype ancestor. In the future, this research could help us better understand the evolution of some of our own higher brain functions and behaviors.

Are you “busy as a bee,” a “social butterfly” or a “fly on the wall”? There are many ways we compare our behavior to that of insects, and as it turns out there may be more to it than just fun idioms. Studying insects could help us understand not only how their behavior has evolved, but also the behavior of highly evolved animals, including ourselves. Mammalian brains are big and complex, so it is difficult to identify which behaviors and neural and genetic changes have co-developed over time. By comparison, insect brains are much smaller and simpler, making them useful models for study.

How hallucinogenic substance in psilocybin mushrooms works on the molecular level

Once it was hot research. Then it was banned. Now, research on psychedelic substances is both hot and legal. There is a revival in psilocybin research in labs and clinics all over the world, including at SDU.
Photo Credit: Artur Kornakov

Psilocybin is a hallucinogenic compound found in about 200 mushroom species, including the liberty cap (Psilocybe semilanceata). For millennia, our ancestors have known and used this substance, and in recent years, it has received renewed interest from scientific researchers and therapists.

The substance has the potential to revolutionize the way we treat conditions such as severe depression and substance addiction, according to many. This is also the opinion of SDU researchers Himanshu Khandelia and Ali Asghar Hakami Zanjani from the Department of Physics, Chemistry and Pharmacy.

The two researchers have recently published the scientific paper The Molecular Basis of the Antidepressant Action of the Magic Mushroom extract, Psilocin. The article is the third in a series on the same topic from the two researchers (Interaction of psychedelic tryptamine derivatives with a lipid bilayer and Magic mushroom extracts in lipid membranes). The newest study's co-authors are Teresa Quynh Tram Nguyen and Luise Jacobsen.