The admissions process is conducted through the Doctoral School website system. The PhD student can apply to this specific project carried out as part of the Warsaw-4-PhD doctoral school via website https://shorturl.at/cJKQY (the application system will be activated from 22nd May, 2023; deadline for sending application is 4th June, 2023). For more information, please follow the link https://shorturl.at/mvxOR
PhD Student
Title: Gut-liver axis in liver cirrhosis (NAWA Polish Returns)
Supervisor: Aleksandra A Kołodziejczyk, PhD
Institute: International Institute of Molecular and Cell Biology in Warsaw
Laboratory: Laboratory of Cellular Genomics
www: https://olab.com.pl/ https://shorturl.at/JNT69
Project description:
Liver is particularly interesting in the context of the microbiome due to its anatomical connection to the gut, where majority of the microbes reside. Together with nutrients from digested food, microbiota-derived molecules and metabolites, reach the liver via portal circulation. This makes the liver uniquely exposed to microbiota, without having direct contact with live bacteria. On the other hand, the liver affects the intestinal environment, directly – for example through bile acid secretion and, more indirectly – for example by regulating metabolic homeostasis of the body. In liver disease such interaction architecture may lead to feedback loops, where liver function deterioration affects the gut physiology or microbiota, which in turn cause exacerbation of the disease.
Liver fibrosis, and its advanced stage - liver cirrhosis, that are the major unmet public health problem in both developed and developing societies. The major aetiologies of liver cirrhosis include prevalent alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD) and viral hepatitis.
In NAFLD and ALD patients, configuration of gut microbes changes due to liver damage and metabolic derangement and particular microbiome signatures were shown to correlate with the disease. These changes are accompanied by variety of gastrointestinal symptoms such as pain, nausea, bloating, diarrhoea or constipation. It is hypothesised that altered microbiota may contribute to disease progression, however there are no studies showing that in a conclusive and mechanistic way. As, up to now, treatment options for liver cirrhosis are very limited, so understanding and reversing pathological changes in the intestine could be an avenue to alleviation of symptoms and potentially limiting disease progression.
Aim:
In this project we aim to examine the gut-liver axis in a mouse model of chronic liver disease, specifically (1) to elucidate the role of microbiota in the progression of liver disease and (2) to understand how liver damage affects microbiota and gut physiology. To address these questions, we will use in vitro and in vivo models of disease and its aspects and advanced genomics (such as single cell RNA sequencing, metagenomics) and bioinformatics.
Requirements:
Position 1
- MSc degree in biology, biotechnology, biochemistry, genetics, medicine or related field
- Knowledge of molecular and cell biology
- Proficiency in written and spoken English
- excellent interpersonal skills, initiative, good work organization, good collaboration skills
- Hands-on experience in laboratory work
- Prior experience in following techniques will be an advantage (but not prerequisite):
- sequencing libraries generation (Illumina, RNAseq, single cell genomics, metagenomics)
- cell culture (cell lines, organoids, CRISPR-based cell line modification techniques)
- microbiology (culturing bacterial isolates, phenotyping, working anaerobically)
- working with mice
- FACS, cell sorting
Position 2
- MSc or MEng degree in biology, biotechnology, engineering, computer science, mathematics, physics or related fields
- Interest in molecular biology and physiology
- Proficiency in written and spoken English
- Excellent interpersonal skills, initiative, good work organization, good collaboration skills
- Ability to code in R and/or Python
- Experience in data science
- Prior experience in Illumina sequencing data analysis or writing pipelines will be an advantage
Number of positions available: 2
Contact: This email address is being protected from spambots. You need JavaScript enabled to view it.
PhD Student
Title: Structural studies of herpesvirus proteins involved in DNA replication
Supervisor: Professor Marcin Nowotny, Auxiliary supervisor: Małgorzata Figiel, PhD
Institute: International Institute of Molecular and Cell Biology in Warsaw
Laboratory: Laboratory of Protein Structure
Project description:
Herpesviruses are among the most widespread human pathogens. They establish lifelong infection with lytic and latent stages. Herpesviruses do not pose a major threat for healthy individuals, but they can cause severe diseases in immunocompromised patients. Most antiviral drugs that are used to treat symptoms of herpesvirus infections disrupt the process of viral DNA replication. The DNA replication mechanism in herpesviruses is largely conserved. It requires six conserved viral proteins: single-stranded DNA-binding protein, three proteins that form the helicase/primase complex, and polymerase and its associated processivity factor. Together, they constitute a macromolecular assembly called the replisome. The initiation of replication appears to be less conserved. In herpes simplex virus type 1 (HSV-1), the best studied herpesvirus, it requires an origin-binding protein.
Despite a wealth of biochemical data on herpesvirus replication proteins, our understanding of herpesvirus DNA replication is still incomplete. No structures have yet been determined for several of the replication proteins. Furthermore, unclear is how replication proteins are recruited to the replication fork and how the synthesis of both DNA strands is coupled. Finally, structural information about interactions of proteins that form HSV-1 replication machinery with each other and with their nucleic acid substrates is missing, so the architecture of the complete replisome or even its parts is unknown.
Aim:
In this project, we aim to improve our understanding of the process of DNA replication in herpesviruses. We plan to achieve this by determining atomic structures of herpesvirus proteins involved in DNA replication and their complexes with relevant nucleic acid substrates using cryo-electron microscopy (cryo-EM) and X-ray crystallography. These structural studies will be complemented by biochemical experiments. Based on the structures and the biochemical data we will reveal how the herpesvirus replisome works and how the activity of its components is regulated and coordinated. The results of this project will be a valuable resource for future efforts that seek to produce new anti-herpesvirus drugs.
Requirements:
- MSc degree in biology, biochemistry or related field
- Solid knowledge of the principles of molecular biology and biochemistry
- Hands-on experience in laboratory work and knowledge of basic molecular biology techniques
- Prior experience in recombinant protein expression, protein purification, X-ray crystallography or electron microscopy will be an advantage
- Proficiency in written and spoken English
- Excellent interpersonal skills, initiative, good work organization
Number of positions available: 2
Contact: This email address is being protected from spambots. You need JavaScript enabled to view it.