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The Laboratory of Dr. Constantinos Patinios

Research AREA: Next-generation genome editing tools based on replication stalling

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The Patinios Lab was established in December 2024 under the leadership of Dr. Constantinos Patinios. It is one of six inaugural research groups comprising the EMBL Partnership Institute at the Vilnius University Life Sciences Center. The Partnership is centered on developing novel genome editing technologies through in vivo and in vitro research.

We have only scratched the surface of the microbial world, as many microbes remain intractable to genetic manipulation. This limitation led researchers to focus on the most tractable rather than the most interesting or valuable microorganisms. In our lab, we want to change this norm by developing widely applicable, user-friendly, and minimalistic genome editing tools that can be applied across the microbial world. Achieving this goal will allow us to advance research areas such as microbiome research, synthetic biology, and industrial microbiology, driving parallel innovation in healthcare and biotechnology.

Our group focuses on discovering, repurposing, and applying genome editing technologies that, amongst other effects, cause replication stalling and trigger the endogenous repair machinery towards homologous recombination and base mutagenesis. With our in-house generated portfolio of genome editing tools, we further delve into the understudied fundamentals of modification-specific replication fork stalling and repair. In-depth knowledge of these processes will enhance our understanding of how repair mechanisms respond to replication stall. This insight will also uncover novel biological processes, paving the way for the development of next-generation genome editing tools.

List of publications:

https://orcid.org/0000-0002-9306-4593

EMBL PI Journal Club

Each week, the EMBL Partnership Insitute hosts a journal club. It focuses on recent advances in gene editing technologies and applications.

We invite you to join us!

Day and time: Fridays from 10 until 11

Location: R104, VU LSC

Here, you will find students, researchers and faculty that share your excitement for new science.

The Laboratory of Dr. Urtė Neniškytė

Targeted CRISPR-Cas Delivery into Mammalian Nervous System

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About

Urte didelis failas 1

Our aim is to apply genome editing in the mammalian brain by developing delivery techniques, screening for the most suitable Cas enzymes, and using them in mouse models and in human brain tissue, with the potential to translate to clinical developments. We maintain two main lines of research: fundamental investigation of glia-dependent circuit refinement in the developing brain, using genome editing tools to disturb physiological processes or restore pathways affected by neurodevelopmental conditions, as well as developing new tools to deliver genome editors to the brain for translational applications. Using these techniques, we aim to understand the molecular cues for neuron-microglia interactions, synaptic discrimination, and the removal of a subset of synapses during brain maturation. We focus on non-proteinaceous molecules on the synaptic plasma membrane - lipids and glycans - and develop and apply genome editing methods to modulate synaptic pruning pathways. As models, we use genetically modified mice, ex vivo brain tissue cultures, and iPSC-derived brain cells. We supplement them with the secondary use of surgically resected human brain tissue for direct investigations of human neurons and glial cells. To support our need to efficiently deliver genome editors into the brain, we collaborate with local and international partners who focus on viral and non-viral gene delivery tools. We have a facility for packaging adeno-associated virus and herpesviral vectors, and are currently working with international collaborators to include adenoviruses in our toolkit. By applying genome editing tools for monogenic disorders with strong neuropathological phenotypes, we contribute to developing proof-of-principle repair of point mutations to provide invaluable insights into the efficacy and targeted delivery of the therapeutic payloads. We expect the established workflows to serve in the future as a paradigm for the preclinical development of CRISPR therapies for various genetic disorders.

The Laboratory of Dr Jonathan Arias

Research AREA: Targeted Delivery of CRISPR-Cas System and Cell/Immunotherapies

Jonathan Arias 2 The Arias Lab was established in 2022 under the leadership of Dr. Jonathan Arias. It is one of six inaugural research groups comprising the EMBL Partnership Institute at the Vilnius University Life Sciences Center. The Partnership is centered on developing novel genome editing technologies through in vivo and in vitro research.

Regenerative medicine - The use of human induced Pluripotent Stem (iPS) cells for the creation of adult cell types has revolutionized our understanding of developmental biology, and it is prone to drive the next generation of cell-based therapeutics. It is remarkable as it can provide new therapeutic opportunities for a wide range of human diseases. Today, Genome Engineering synergizes with Regenerative Medicine allowing us to confer novel therapeutic functions to cells, yielding "smart-therapeutics". Similarly, Genome Engineering allows us correcting deleterious mutations within our genomes both in vivo and ex vivo.

To fulfill this potential, the Arias lab engineers human iPS cells utilizing cutting-edge nucleases for the creation of cell-based therapeutics with clinical translation potential. This approach allows us to manufacture cells ex vivo and therefore we can introduce therapeutic functions in a reliable manner and perform extensive quality control. Our technologies and expertise include precise genome engineering, lineage-specific differentiation and AI driven biosciences.

We are an inter-disciplinary and international team glad to establish collaborations across the globe to achieve our vision. We invite you to follow us or join us as we pursue the next generation therapeutics!

Learn more about us at Webpage of Group

Contact:

Jonathan Arias, PhD, Group Leader
LSC-EMBL Institute for Genome Editing Technologies
Vilnius University Life Science Center
7 Saulėtekio Ave, LT-10257 Vilnius, Lithuania
E:

Laboratory of Dr Giancarlo Russo

Research AREA: Genome Informatics And Sequencing

Research

Clustered regularly interspaced short palindromic repeats (CRISPR) are arrays of short (ca. 30bp) DNA direct repeats (DR) arranged in an alternating fashion with spacers, which are instead different oligos, of ca. 25-70bp. CRISPR arrays have so far been reported in ca. 50% of bacteria and most archea. The spacers in the array are mobile genetic elements (MGE) which have been acquired upon bacteriophage invasions, and therefore represent a historical record of previous infections. Upstream of the CRISPR array sits a CRISPR-associate (Cas) gene: when a phage injects its DNA through the membrane, Cas genes recruit the appropriate transcribed spacer sequence from the CRISPR array. Such sequence acts as a guide to bind the complex to the viral genome and allows the Cas nuclease to produce a double-strand break, neutralising the viral threat. CRISPR-Cas is a formidable example of acquired immune response.

In the context of genome sequencing, CRISPR research efforts have been based on short reads and, to date, the potential of long-read sequencing technologies for CRISPR-Cas applications has not been throughly assessed.

Our research group, established in September 2021 and led by Dr Giancarlo Russo, focuses on two aspects associated with CRISPR-Cas systems. On the one hand, we investigate the long-term co-evolution of bacteria and phages in vivo, both in isolation and embedded in their natural microbial communities. On the other hand, we explore epigenetic and post-transcriptional changes in cancer cells and their regulating effects on preferential isoforms’ usage, and how such phenotypes are affected by epigenetic editing. The common thread is to leverage the potential of long-read sequencing technologies to identify DNA and RNA modifications and dissect alternative splicing in the context of CRISPR-Cas research.

Group Members

	Giancarlo Russo, Ph.D. Group Leader Following my Master's Degree in Italy and my Ph.D. at Cardiff University, UK, (both in Applied Mathematics), in 2009 I started working on the applications of computational methods in life science. From 2009 to 2011 I held a Research Associate position at the Biostatistics and Bioinformatics Unit of the MRC Centre for Psychiatric Medicine in Cardiff, with a focus on Genome-Wide Association Studies. In the last part of 2011, I moved to Nagoya, Japan, as a visiting researcher at the University Hospital, where we worked on the genetics of schizophrenia. For the following ten years, until July 2021, I have been a senior scientist at the Functional Genomics Center in Zurich, Switzerland, where I have taken part in almost 200 different research projects spanning the whole spectrum of high throughput -omics applications. Publications
	Lina Aitmanaitė, Ph.D. Researcher In 2012, I received a Bachelor's degree in Molecular Biology from Vilnius University. My thesis was about the seasonal polyphenism of Daphnia Pulex. Following my undergraduate studies, I enrolled in a molecular biology master's program. I worked on the thermostabilization of T7 RNA polymerase in vitro as part of my Master's thesis. I then completed my internship at the Erasmus Medical Centre in Rotterdam, where I was able to collaborate with Prof. Vincenzo Bonifati's research on Parkinson's disease. Soon after, I began my Biochemistry Ph.D. studies at Vilnius University. My dissertation research focused on the molecular processes of dsRNA LA and M virus maintenance in yeast cells. The interactions between the LA and M viruses were an important part of my research. In 2021, I successfully defended my PhD thesis, "Virus Compatibility in Saccharomyces cerevisiae LA and M Virus Systems."
	Karolis Širmonaitis Junior Researcher +37064456373 In 2020, I have obtained a Master’s degree in Medical Biotechnology at Wageningen University and Research in The Netherlands. During my studies there, I have worked in a laboratory of applied microbiology which is led by John Van Der Oost, who is a renowned scientist known as one of the pioneers of Crispr-Cas9. My master’s thesis project in this group was aimed at developing a novel, homology based, DNA cloning method. After finishing my thesis project I moved to Switzerland, where I completed an internship in a Biotech company called ‘’Amal Therapeutics’’. The goal of this company is to develop therapeutic vaccines against cancer. During my internship at ‘’Amal therapeutics’’, I have worked in an in vitro department, where I developed and implemented a vaccine potency evaluation protocol on a newly adopted cell line. Soon after, I returned to Lithuania and started working for “ThermoFisher Scientific” as a junior Scientist. While working at this position, I was involved in qPCR and Digital PCR product development and release. In the end of 2021, I joined VU GMC-EMBL PI. Currently, I’m working on a project which explores the relationship between CRISPR-Cas adaptation and genome-wide methylation patterns.
	Kornelija Gelūnaitė Ph.D. Student +37064082011 In 2021, I have graduated with BSc (Hons) degree in IBMS accredited Biomedical Sciences at the University of the West of England (UWE), in Bristol, United Kingdom. In my final year, I have completed a research project module and wrote a thesis on understanding hypoxia and RAS-ERK signalling in pancreatic cancer and identifying novel therapeutic targets. After completion of BSc, I have continued my education in UWE and in 2022, I have purchased Master of Research (MRes) degree, where I have worked on targeting GPCRs in the pancreatic cancer in autophagy and hypoxia in collaboration with Dr. Alexander Greenhough in CRIBBS lab. Currently, I’m undertaking Ph.D. in Biology at Vilnius University, LSC as part of EMBL team with a project that focuses on full-length, targeted sequencing of CRISPR-Cas systems in microbial ecosystems.
	Domantas Palavenis My life sciences journey started in Vilnius University. Here I graduated from Genetics BSc and garnered necessary fundamental knowledge about life sciences. During my senior year I deepened my comprehension about plant genetics while working in VU Botanical Garden and writing my final thesis there. The latter one involved molecular and bioinformatical applications in order to genetically compare a wild type Lolium perenne and its mutant. After the graduation I decided make a fresh start and broaden my horizons in a different field. I ended up in MSc of Molecular Biotechnology and I joined the team of EMBL PI led by Dr. G. Russo. This time I am going to give a shot to epigenome editing using catalytically inactive dCas9 protein and DNA methyltransferases.
	Gediminas Gumbis In 2021, I graduated from the University of Edinburgh with a bachelor's degree in Biological Sciences (Biochemistry). I conducted my honours project at the lab of P. Uhlén at Karolinska Institute, Sweden. The aim of the project was to analyse spontaneous Calcium signals in HeLa cells. After graduating, I worked for about a year at ThermoFisher Scientific Baltics as a junior microbiologist. In September 2022, I started studying Medicine at Vilnius University. I joined EMBL in October 2022.

Career at LSC-EMBL PI

Laboratory of Dr Stephen Knox Jones is looking for a postdoctoral researcher and Ms or PhD student. More information on the Jones!Lab website.

EMBL PI Contacts

Dalia Lukšienė
Administration Manager
Room C145, Saulėtekio al. 7, Vilnius

+370 5 2234426

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Subcategories

Cell Therapeutics

Genome Informatics And Sequencing