Topic: Enhancing the Biocompatibility of Rhodamine Fluorescent Probes by Positional Isomerism Approach

Fluorescence microscopy is an essential tool for understanding dynamic processes in living cells and organisms. Many fluorescent probes for labeling cellular structures suffer from unspecific interactions and low cell permeability.

We found that isomeric tuning could optimize rhodamine fluorescent probes’ biocompatibility without affecting their photophysical properties.

Later, we discovered that the neighboring group effect in novel isomer-4 rhodamines dramatically increases cell permeability of the rhodamine-based probes by stabilizing a fluorophore in a hydrophobic spiro-lactone state. However, 1^st generation synthetic route to 4-carboxyrhodamines was based on Pd catalyzed fluorescein to rhodamine conversion, which limited structural diversity and had multiple protection and deprotection steps.

Recently we have developed 2^nd generation protecting group free synthesis route for 4-carboxyrhodamine class fluorescent dyes. This approach drastically reduces the number of synthesis steps, expands the achievable structural diversity, increases overall yields, and permits gram-scale synthesis of the dyes.

By employing this synthetic route, we synthesized and characterized a wide range 4-carboxyrhodamines and targeted them to multiple targets in living cells.

Topic: Harnessing Nature: Mental Health Treatments through Metabolic Engineering and Synthetic Biology

Advances in metabolic engineering and synthetic biology are opening new avenues for developing next-generation psychiatric treatments by harnessing natural molecules from diverse biological kingdoms.

Compounds derived from fungi, such as mushroom alkaloids, have gained attention for their potential to treat mental health disorders, including treatment-resistant depression and anxiety.

By recreating and optimizing the biosynthetic pathways of these bioactive molecules, we can scale their production in genetically modified organisms like yeast, enabling more sustainable and controlled manufacturing processes.

This approach is not limited to fungi. Other natural sources, including plants contain promising small molecules with neuroactive properties that can be explored as breakthrough therapies. The integration of these natural compounds with advanced engineering techniques offers the potential to uncover novel mechanisms of action that target the brain’s complex chemistry in innovative ways.

As we explore these therapeutic candidates, there is growing potential to deliver more precise, personalized psychiatric treatments with fewer side effects compared to traditional drugs. This convergence of nature and science holds promise for the future of mental health care, offering a new wave of therapies that address the global mental health crisis.

Topic: Astral – a Cutting-Edge Platform for Multi-Omics Applications
2024 Global R&D 100 Winner

This year, a cutting-edge plaform for multi-omics applications was recognized as one of TOP100 most innovative technologies in the global prestigious R&D 100 Awards. The R&D 100 Awards is the only science and technology awards competition that recognizes new products and technologies for their technological significance.

The Orbitrap Astral platform is an advanced tool designed for comprehensive multi-omics analyses, encompassing genomics, proteomics, metabolomics, and lipidomics. Utilizing state-of-the-art mass spectrometry with the highly accurate Orbitrap mass analyzer, it offers exceptional resolution and sensitivity.

This platform enables detailed molecular profiling and quantification, facilitating simultaneous multi-omics workflows. By streamlining data acquisition and analysis, the Orbitrap Astral platform accelerates research in biomarker discovery, disease mechanisms, and therapeutic development, setting a new standard for multi-omics investigations.

Topic: Cell-based Therapeutics Development: from Idea to the Patient

The intersection of medicine, biology, pharmaceuticals, and biotechnology represents a dynamic field for innovations.

There is a constant and focused effort to transform laboratory challenges into tangible medical treatments that reach the patient.

Innovative solutions such as cells and exosomes are developed for acute conditions such as kidney injuries, illustrating strategies to manage these conditions.

Additionally, the advancement of treatments for debilitating chronic diseases, such as degenerative joint and skin conditions aim to enhance patient quality of life and longevity.

These developments play a crucial role in improving overall health and wellness, marking a pivotal shift from ideas to impactful patient care.

Topic: Novel Cell Isolation Platform with Active-Release Technology
2024 global R&D 100 Winner

This year, novel platform was recognized as one of TOP100 most innovative technologies in the global prestigious R&D 100 Awards. The R&D 100 Awards is the only science and technology awards competition that recognizes new products and technologies for their technological significance.

Cell therapy development and manufacture represents a transformative approach in modern medicine, offering potential cures for various conditions, including cancer and genetic disorders.

However, the generation of cell-based therapies deals with specific challenges, mainly, scalability, consistency, and regulatory compliance, which impact not only developers but patients as well. Addressing these pain points requires innovative solutions such as controllable cell activation process combined with automated and closed-system manufacturing, that are flexible and scalable.

Building upon our established Dynabeads™ and CaptureSelect™ technologies, the new Detachable Dynabeads feature an innovative active release mechanism.

The cell marker specific VHH ligands are conjugated to a low-affinity biotin derivative, allowing bead detachment from target cells via the competitive binding of biotin in the release buffer.

Optimized for the Gibco™ CTS™ DynaCellect™ Magnetic Separation System, this technology enables full automation and scalability in process development and clinical manufacturing.

Topic: Paving the Road Towards Universal Microbial Genome Editing

Microbe genome editing remains constrained by complex, time-consuming, and often inefficient protocols. These attributes render genome editing, particularly in non-model organisms, a technically challenging and frequently unsuccessful endeavour.

In my group at VU-EMBL PI for genome editing technologies, we reconstruct the genome editing pipeline by developing simple, efficient and widely applicable genome editing tools. As an example, I will showcase SIBR-Cas and Append Editing.

SIBR is a gene expression system which can control the expression of any gene of interest in virtually any mesophilic prokaryote of interest. We used SIBR to control the expression of the CRISPR-Cas9 and CRISPR-Cas12a proteins in various wild type bacteria, achieving high editing efficiencies. Append Editing is a novel CRISPR-based tool that appends bulky ADP-ribosyl moieties to DNA bases, causing stall of DNA replication and resulting in DNA recombination.

We used Append Editing to install small size (~90 bp) substitutions, insertions or deletions in the genome of E. coli, with high editing efficiency and without a reduction in resulting colonies. Moreover, we tested Append Editing in eukaryotic cells (yeast, tobacco and human cells) and noticed that, in contrast to bacteria, site-specific ADP-ribosylation drives replacement of the modified DNA base.

Topic: Understanding Human Existence through Viruses

The human body is host to many pathogens living a symbiotic life within our body. Understanding the molecular mechanism and strategies these pathogens use for their survival provides us a unique opportunity to understand our own existence.

Human herpesviruses are one such group of large double stranded DNA viruses. Herpesviruses establish lifelong latency upon primary infection in human. Human herpesvirus 6 (HHV-6) and HHV-7 establish latency by integrating into the host telomere, which is sometimes genetically inherited.

Productive virus reactivation is rare, but its clinical associations with diseases are well-recognized. HHV-6, like other herpesviruses, frequently undergo abortive reactivation where the virus life cycle is never completed. The pathological effects of abortive HHV-6 reactivation remain elusive.

Recently, in a groundbreaking study, we reported that the HHV-6-encoded miRNA, miR-aU14, exploits miRNA-mediated inhibition of miRNA processing as a so far unknown cellular mechanism to disrupt mitochondrial architecture, evade the induction of type I interferons, and facilitates virus reactivation.

We have established a new research group at RSU, Latvia focusing on developing systems biology-based approaches that allows us to understand complex host-pathogen interactions at single-cell to organoid levels. This talk will introduce the audience to some of our innovative experimental approaches that we develop and use within our group.

Topic: Precision Medicine

Precision medicine (PM), a field of medicine rapidly gaining popularity in the world, is changing the traditional treatment and prevention of diseases in countries.

PM is made possible by the invention of new technologies and their application to clinical activity, as well as the possibility of evaluating disease-causing changes at the molecular genetic level.

Thanks to these innovations, the healthcare systems of countries around the world have begun to change their approach to patients, and a standardized approach is not always the right step on the path to successful treatment. People differ in their genetic characteristics, lifestyle, and risk of developing certain diseases.

Thus, PM aims to select the most optimal treatment method and takes into account the unique characteristics of each patient.

Diagnostics based on molecular genetic tests allow faster identification of risks that threaten a person’s health, strengthen the prevention of serious diseases, and reduce long-term costs for complications, disease progression, or patient hospitalization.

Topic: Novel Cell Isolation Platform with Active-Release Technology
2024 global R&D 100 Winner

This year, novel platform was recognized as one of TOP100 most innovative technologies in the global prestigious R&D 100 Awards. The R&D 100 Awards is the only science and technology awards competition that recognizes new products and technologies for their technological significance.

Cell therapy development and manufacture represents a transformative approach in modern medicine, offering potential cures for various conditions, including cancer and genetic disorders.

However, the generation of cell-based therapies deals with specific challenges, mainly, scalability, consistency, and regulatory compliance, which impact not only developers but patients as well. Addressing these pain points requires innovative solutions such as controllable cell activation process combined with automated and closed-system manufacturing, that are flexible and scalable.

Building upon our established Dynabeads™ and CaptureSelect™ technologies, the new Detachable Dynabeads feature an innovative active release mechanism.

The cell marker specific VHH ligands are conjugated to a low-affinity biotin derivative, allowing bead detachment from target cells via the competitive binding of biotin in the release buffer.

Optimized for the Gibco™ CTS™ DynaCellect™ Magnetic Separation System, this technology enables full automation and scalability in process development and clinical manufacturing.