Uncategorized
AI Predicts Gene Regulation for Drug Discovery Using Condensate Morphology
In a study published in Cell titled, “Deep learning of functional perturbations from condensate morphology,” researchers at Princeton University have applied AI to understand how drugs affect the dynamics of key structures within the cell. The work introduces a tool that can map morphology to functional outcomes and shed light on markers of health.
The authors examined the changes in shape of biomolecular condensates, tiny droplets in cells that drive transcription and other gene regulation processes linked to disease, including Alzheimer’s, ALS and cancer. The findings support a robust system for monitoring and evaluating cellular responses to drugs at a single-cell level.
“The central problem in biology is how do you get emergent structure from individual molecular interactions,” said Cliff Brangwynne, PhD, professor of chemical and biological engineering at Princeton and corresponding author of the study. “The key innovation here was to develop a way to learn from the images and classify the patterns that are emergent.”
The team used an advanced microscope to image nucleolar morphology changes in hundreds of human cells under a range of drug-controlled conditions. Machine learning tools sorted the images into four basic categories based on the shape of the nucleolus, uncovering “cap” and “necklace” shapes linked to cellular stress responses.
The authors ran a panel of drugs to examine the effect on nucleolar formation and measured changes in the condensate’s development. Varying concentrations caused different degrees of change in both caps and necklaces.
Two known anti-cancer drugs caused caps, while a third drug, called topotecan, triggered a new nucleolus morphology that the researchers labeled “flower.” While topotecan inhibits TOP1, an key enzyme during DNA replication, loss of TOP1 induced the flower shape and uncovered the enzyme’s role in maintaining nucleolar organization by regulating RNA processing.
“No one’s seen this flower morphology before,” said Brangwynne. “The network flagged it as not fitting neatly into the other three categories.”
The team also tested their neural network on other condensates related to RNA processes, observing similar dose-and-response results for drugs specific to nuclear speckles, a hub for messenger RNA activity, and condensates from respiratory syncytial virus.
This finding underscores the value of analyzing morphological changes. “You could be missing other important features,” said Anita Donlic, PhD, postdoctoral researcher and first author of the study. “Things that could tell you there’s new biology.”
The post AI Predicts Gene Regulation for Drug Discovery Using Condensate Morphology appeared first on GEN – Genetic Engineering and Biotechnology News.
Hosted by Drug Discovery World and supported by Sartorius and BioIVT, this webinar will explore the opportunities and challenges that exist within cancer research drug discovery and development.
You will hear from Dr Sudha Rao, Chief Scientific Officer of Kazia Therapeutics, Karol Budzik, PhD, Business Development Associate at Vyriad Therapeutics and Lars van der Veen, Chief Scientific Officer at iOnctura.
Presentations will cover how cancer treatments have shifted towards reprogramming the biology driving tumour growth, immune escape and treatment resistance, the trajectory that in vivo CAR-T treatments are taking, and how challenging tumours burdened by stroma and immune-mediated resistance can be tackled.
Q&A with the speakers follows the presentations.
The post New webinar: Tackling drug discovery challenges in cancer research appeared first on Drug Discovery World (DDW).
Amid the rise of psychedelics in the mental health space, researchers have begun to explore psilocybin as a treatment for chemotherapy-induced peripheral neuropathy.
Uncategorized
New Spectrometry Technique Could Aid Formulation Development
New Spectrometry Technique Could Aid Formulation Development
A new technique combining two forms of spectrometry could help biopharmaceutical companies improve their choice of formulation buffer for antibody manufacturing by revealing how molecular forms and three-dimensional shapes of complex biologics respond to their environment. That’s the view of Christian Bleiholder, PhD, a professor at Florida State University who helped develop the technique.
According to Bleiholder, what happens structurally when a complex biological molecule, such as an antibody or viral spike protein, binds to its target is currently poorly understood.
“This is where [this approach] can help with the bioprocessing and formulation,” he says, as structural changes “can affect the lifespan [of the product] and lead to issues, such as aggregation.”
Because antibodies are complex, existing techniques tend to be powerful at different levels of complexity, he explains. Mass spectrometry is particularly powerful for distinguishing molecular composition, while structural approaches such as X-ray crystallography and cryo-electron microscopy can provide high-resolution structural information.
The challenge is understanding the link between these things within a heterogeneous sample, he says.
To overcome this, Bleiholder and his team worked with Bruker Daltonics to develop Tandem-Trapped Ion Mobility Spectrometry (Tandem-TIMS). This combines tandem ion mobility spectrometry with tandem mass spectrometry to disentangle three overlapping layers of molecular complexity: molecular form, three-dimensional shape, and binding or assembly state, he says.
He explains that, if the proteins have different structures, they can be characterized with tandem ion mobility spectrometry, and then mass spectrometry can be used to look at their molecular forms and binding states.
Going forward, Bleiholder hopes the technique can be used for formulation development but also earlier, during drug discovery of new products, such as multi-specific antibodies, to determine which molecular states are important and how those change when a biologic engages its target. He also plans to look at automating the technique.
Bleiholder spoke about using Tandem-TIMS at the Bioprocessing Summit in Boston earlier this year.
The post New Spectrometry Technique Could Aid Formulation Development appeared first on GEN – Genetic Engineering and Biotechnology News.
BIO’s plan for ‘securing America’s biotech century’
China’s innovation moment sees a rise in first in class
Windward prices IPO, Rezera postpones its offering: Finance Report
FDA Approves First Drug to Treat Adults with Primary Membranous Nephropathy
How Vancomycin-Resistant Enterococcus Evolved in a Danish Hospital
Cellectis could cut 70% of workforce in shift to in vivo therapies
-
Uncategorized8 months agoNovartis buys Synnovation’s PI3Kα inhibitors for $3 billion
-
Endpoints News8 months ago
Novartis to pay $2B upfront to take next-gen PI3Kα inhibitor from Synnovation
-
Uncategorized6 months agoOptical Pooled CRISPR Screen Reveals Regulators of NF-κB Dynamics in Human Cells
-
Uncategorized6 months ago
Relay’s PI3Kα inhibitor clears efficacy bar in Phase 2 vascular anomalies study
-
Uncategorized5 months ago
Hybrid solid−liquid optics enable scalable, high-resolution light-sheet microscopy across diverse immersion media
-
Fierce Biotech8 months ago
Scientists turn pig semen extract into eye drops that kill cancer in mice
-
Nature Biotechnology8 months ago
Sustained nitric oxide production by engineered E. coli remodels the tumor microenvironment and potentiates immunotherapy
-
BioPharma Dive – AI / Data8 months agoAstraZeneca lung drug gets ‘surprise’ win in COPD trials
Scan to Read