Lifeboat Foundation

Researchers at the University of Chicago’s Pritzker School of Molecular Engineering (PME), Argonne National Laboratory, and the University of Modena and Reggio Emilia have developed a new computational tool to describe how the atoms within quantum materials behave when they absorb and emit light.

The tool will be released as part of the open-source software package WEST, developed within the Midwest Integrated Center for Computational Materials (MICCoM) by a team led by Prof. Marco Govoni, and it helps scientists better understand and engineer new materials for quantum technologies.

“What we’ve done is broaden the ability of scientists to study these materials for quantum technologies,” said Giulia Galli, Liew Family Professor of Molecular Engineering and senior author of the paper, published in Journal of Chemical Theory and Computation. “We can now study systems and properties that were really not accessible, on a large scale, in the past.”

Targeted protein degradation (TPD) is an emerging therapeutic modality and has attracted great attention from academia and industry^1,2. The prototypical TPD agents, molecular glues (MGs) and proteolysis targeting chimeras (PROTACs), can lead to temporal proteasomal degradation of the protein-of-interest (POI). PROTACs are small heterobifunctional molecules integrating an E3-ligase binder and a POI binding moiety through a synthetic linker construct. The PROTACs technology has been applied to degrade numerous pathological proteins and a rich pipeline is currently progressing into preclinical and early clinical trials^3,4,5. However, overcoming PK/PD issues towards clinical compounds is demanding due to the intrinsically high molecular weight and related physicochemical properties⁶. On the other hand, MGs are small molecules with beneficial ‘drug-like’ physicochemical properties binding to an E3 ligase, and, similarly to PROTACs, leading to neosubstrate proteasomal degradation. Their mechanism of action is however less predictable; their often hydrophobic surface-exposed portions of the MGs seem to change the hydrophobic surface area of the E3 ligase and thereby leading to neosubstrate ubiquitination and degradation^7,8. MGs have already proven their validity as marketed drugs, as there are several approved drugs or clinical compounds working by an MG mechanism (Fig. 1A), for example, the IKZF1/3 degrader thalidomide and its analogs pomalidomide and lenalidomide⁸, and the RBM39 degrader indisulam⁹. Thalidomide analogs induce selective ubiquitination and degradation of two lymphoid transcription factors, IKZF1 and IKZF3, by the CRBN-CRL4 ubiquitin ligase¹⁰. Additionally, CSNK1A1 (CK1α) was recently discovered as a lenalidomide-specific neo-substrate¹¹. Interestingly, modification of pomalidomide or lenalidomide can have a profound impact on the degradation potency and degradation profiles. For example, CC-220 (Fig. 1A) showed 10-fold more potency in the cells than lenalidomide, and CC-885 (Fig. 1A) was found to induce degradation of the substrate GSPT1^12,13. Both MGs and PROTACs are emerging drug modalities providing interesting features over classical pharmacology-driven drugs by their ability to drive the destruction of proteins that have multiple functions, thereby potentially overcoming resistance mechanisms and providing new pharmacology. While PROTACs can be developed highly rationally, MGs are discovered rather serendipitously requiring synthesis and testing of large series of compounds^14,15. Additionally, the discovery of MGs and PROTACs is done in a sequential, often mmol scale synthesis which is time-consuming and expensive.

In this work, to address current shortcomings in MGs discovery, we use the direct-to-biology (D2B) approach and combined the automated, high throughput miniaturized synthesis with cell-based phenotypic screening (Fig. 1B). The I.DOT (Immediate Drop on Demand Technology, a pressure-based nano dispensing technology) is employed to accelerate the synthesis of diverse MGs libraries on nano scale^{16,17,18,19,20,21}. In a subsequent cell-based phenotypic screening cascade, the compounds are tested in the thalidomide and analog sensitive MM.1S multiple myeloma cell line which reportedly is used for MGs screening²². In this D2B screening platform, the crude compounds are directly screened on cells without further chromatographic purification or clean up. Then, the 19 best compounds are selected for re-synthesis on mmol scale followed by purification and fully characterized.

A biohybrid, leaf-spring design of DNA origami functions as a pulsating nanoengine that exploits the DNA-templated RNA transcription mechanism while consuming nucleoside triphosphates as fuel. The nanoengine also drives a nanomechanical follower structure.

When it comes to delivering drugs to the body, a major challenge is ensuring that they remain in the area they’re treating and continuing to deliver their payload accurately. While major strides have been made in delivering drugs, monitoring them is a challenge that often requires invasive procedures like biopsies.

Researchers at NYU Tandon led by Jin Kim Montclare, Professor of Chemical and Biomolecular Engineering, have developed proteins that can assemble themselves into fibers to be used as therapeutic agents for the potential treatments of multiple diseases.

These biomaterials can encapsulate and deliver therapeutics for a host of diseases. But while Montclare’s lab has long worked on producing these materials, there was once a challenge that was hard to overcome—how to make sure that these proteins continued to deliver their therapeutics at the correct location in the body for the necessary amount of time.

A non-organic intelligent system has for the first time designed, planned and executed a chemistry experiment, Carnegie Mellon University researchers report in the journal Nature (“Autonomous chemical research with large language models”).

The delivery of drugs to specific target tissues and cells in the brain poses a significant challenge in brain therapeutics, primarily due to limited understanding of how nanoparticle (NP) properties influence drug biodistribution and off-target organ accumulation. This study addresses the limitations of previous research by using various predictive models based on collection of large data sets of 403 data points incorporating both numerical and categorical features. Machine learning techniques and comprehensive literature data analysis were used to develop models for predicting NP delivery to the brain. Furthermore, the physicochemical properties of loaded drugs and NPs were analyzed through a systematic analysis of pharmacodynamic parameters such as plasma area under the curve. The analysis employed various linear models, with a particular emphasis on linear mixed-effect models (LMEMs) that demonstrated exceptional accuracy. The model was validated via the preparation and administration of two distinct NP formulations via the intranasal and intravenous routes. Among the various modeling approaches, LMEMs exhibited superior performance in capturing underlying patterns. Factors such as the release rate and molecular weight had a negative impact on brain targeting. The model also suggests a slightly positive impact on brain targeting when the drug is a P-glycoprotein substrate.

Researchers at the University of Sussex have discovered the transformative potential of Martian nanomaterials, potentially opening the door to sustainable habitation on the red planet.

Using resources and techniques currently applied on the International Space Station and by NASA, Dr. Conor Boland, a Lecturer in Materials Physics at the University of Sussex, led a research group that investigated the potential of nanomaterials—incredibly tiny components thousands of times smaller than a human hair —for clean energy production and building materials on Mars.

Taking what was considered a waste product by NASA and applying only sustainable production methods, including water-based chemistry and low-energy processes, the researchers have successfully identified electrical properties within gypsum nanomaterials—opening the door to potential clean energy and sustainable technology production on Mars.

For instance, the pegRNA molecules used in prime editing are difficult and expensive to chemically synthesise or laborious to clone, which hampers the crucial optimisation of prime-editing efficiency. Additionally, the reverse transcriptase (RT) enzymes used in prime editing are relatively error-prone and have low processivity, which may limit the precision and size of edits that can be introduced. Furthermore, RTs have a low affinity for dNTPs, which can impact prime-editing efficiency in non-dividing and differentiated cells.

To address these issues, two research groups led by Dr. Ben Kleinstiver at Mass General Hospital (MGH) & Harvard Medical School, and Dr. Erik Sontheimer at the RNA Therapeutics Institute (UMass Chan Medical School) have independently developed new approaches that build upon prime editing by replacing RT with another type of enzyme, namely a DNA-dependent DNA polymerase. This change permits the use of DNA instead of RNA as a template for editing, potentially addressing some of the main limitations of prime editing by allowing higher efficiency and adaptability.

A “chaperone” molecule that slows the formation of certain proteins reversed disease signs, including memory impairment, in a mouse model of Alzheimer’s disease, according to a study from researchers at the Perelman School of Medicine at the University of Pennsylvania.

In the study, published in Aging Biology, researchers examined the effects of a compound called 4-phenylbutyrate (PBA), a fatty-acid molecule known to work as a “chemical chaperone” that inhibits protein accumulation. In mice that model Alzheimer’s disease, injections of PBA helped to restore signs of normal proteostasis (the protein regulation process) in the animals’ brains while also dramatically improving their performance on a standard memory test, even when administered late in the disease course.

“By generally improving neuronal and cellular health, we can mitigate or delay disease progression,” said study senior author Nirinjini Naidoo, Ph.D., a research associate professor of Sleep Medicine. “In addition, reducing proteotoxicity— irreparable damage to the cell that is caused by an accumulation of impaired and misfolded proteins—can help improve some previously lost brain functions.”