Dr Pravin Jagtap

Supervisor Details

Contact Details

School of Biosciences, University of Birmingham

Scientific Background

Research Interests

The Jagtap Lab investigates the molecular mechanisms of protein-RNA complexes central to human health and disease, with a particular emphasis on RNA helicases—enzymes critical for unwinding RNA during cellular processes. Dysregulation of these helicases contributes to various diseases, yet developing selective therapeutics remains difficult because of their conserved ATP and RNA binding sites. To address this, the lab explores novel, transient druggable sites by studying the regulatory roles of accessory RNA-binding domains (RBDs) within helicases. Building on our previous discoveries that reveal how RBDs can toggle the activity of the RNA helicase MLE “on” or “off”, the team aims to determine whether similar regulatory mechanisms exist across other helicases.

Using a multidisciplinary approach that combines structural biology, biochemistry, and cellular studies, our lab seeks to understand how RBDs modulate helicase function, alter RNA target specificity, and reshape protein interaction networks. The lab’s ultimate goal is to leverage this mechanistic insight to develop small-molecule modulators capable of correcting helicase dysfunction in disease. Through collaboration and innovation, the lab strives to translate fundamental discoveries into therapeutic strategies that enhance human health and deepen our understanding of RNA helicase regulation.

Research Groups

Jagtap Lab

Supervision Style

In three words or phrases: Outcome-oriented, supportive, collaborative.

Provision of Training

In your first year, either I or an experienced postdoc in the lab will help with your technical training. As you gain confidence, you’ll gradually become independent, with the goal of working fully on your own by the second year.

Progression Monitoring and Management

You’ll be encouraged to take ownership of your progression, while we will discuss clear expectations on a monthly basis. If challenges arise or goals aren’t fully met, we’ll work together to troubleshoot and create a plan of action.

Communication

I don’t expect anyone in the team to communicate outside of working hours. That said, I’m always here if you need support, and I’m happy to talk through any issues or offer advice whenever it’s helpful.

Meetings

PhD Students can expect scheduled meetings with me at least once per week. These meetings will be face-to-face. I am usually contactable for an instant response 3 or 4 days per week.

Work Patterns

The timing of work in my lab is completely flexible, and (other than attending pre-arranged meetings), I expect students to manage their own time.

Notice Period for Feedback

I need at least 1 week's notice to provide feedback on written work of up to 5,000 words.

MIBTP Project Details

Primary supervisor for:

How RNA Helicases Work: Mapping Regulatory Sites on DHX29

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

How RNA Helicases Work: Mapping Regulatory Sites on DHX29

University of Registration: University of Birmingham

BBSRC Research Themes:

Understanding the Rules of Life (Structural Biology)

Project Outline

"RNA helicases are ATP-dependent RNA unwinding enzymes essential for RNA metabolism. Their central role in cellular function links their dysregulation to numerous diseases, including cancer and neurodegeneration. Despite their therapeutic potential, selective targeting of helicases is challenging because of the highly conserved ATP and RNA binding sites among proteins. Interestingly, many eukaryotic helicases also contain small RNA-binding accessory domains beyond the conserved helicase core. Our recent work showed these domains do more than bind RNA: they regulate the helicase by interacting with the core, switching activity on or off. This core–accessory interface presents alternative, potentially druggable sites beyond conserved ATP and RNA binding regions.

One such RNA helicase DHX29 is critical for translation control, and its depletion inhibits tumor growth, making it a promising cancer target. DHX29 possesses an N-terminal double-stranded RNA-binding domain in addition to the helicase core, providing a unique opportunity to study regulatory interactions between these domains.

This project will have following aims to identify novel regulatory sites on DHX29 for selective targeting:

1. Structural characterization – Solve DHX29 structures in multiple states (apo, ATP/ADP-, ssRNA-, dsRNA-bound) to capture conformational dynamics.

2. Domain interactions – Investigate how the dsRNA-binding domain communicates with the helicase core using biophysical approaches.

3. Functional validation – Use mutagenesis and RNA unwinding/binding assays to confirm regulatory mechanisms.

This multidisciplinary study will provide a comprehensive atomic and molecular view of DHX29’s helicase cycle. By mapping transient regulatory sites, the project aims to reveal druggable regions distinct from conserved ATP and RNA binding pockets, potentially enabling selective small-molecule therapeutics for misregulated helicases in cancer and other diseases.

APPLY HERE

Structural and Functional Dissection of the U1–RNA–PAP Complex in Viral Gene Regulation

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Structural and Functional Dissection of the U1–RNA–PAP Complex in Viral Gene Regulation

Secondary Supervisor(s): Prof Jo Parish

University of Registration: University of Birmingham

BBSRC Research Themes:

Understanding the Rules of Life (Structural Biology)

Project Outline

Background and Rationale:

Precise regulation of viral gene expression is critical for productive infection, ensuring that early and late viral genes are expressed at the correct stage of viral life cycle. For eg. in bovine papillomavirus-1 (BPV-1), early genes initiate replication, while late genes required for virus particle formation remain repressed until later. A major mechanism underlying this regulation involves U1 snRNP (U1) complex, a core component of the host splicing machinery, and particularly the U1-70K protein which is part of the U1 snRNP.

Studies show U1-70K suppresses late viral gene expression by blocking polyadenylation. Bound U1-70K inhibits poly(A) polymerase (PAP), preventing maturation of late pre-mRNAs and directing them to degradation pathways. Similar mechanisms exist in HPV16 and HIV, emphasizing U1-70K as a conserved regulator. Yet, the molecular details of U1-70K–PAP interaction remain unknown. Open questions include whether U1 simply positions U1-70K near PAP or whether binding triggers conformational changes exposing key sites, and how the U1–RNA–PAP complex is structurally organized. Addressing these questions will illuminate how viruses hijack host RNA processing and inspire therapeutic strategies.

Aims:

This project seeks to uncover how U1-70K represses HPV gene expression by:

1. defining domains and affinities of U1-70K–PAP interaction;

2. assembling and structurally characterizing the U1–RNA–PAP complex;

3. Testing the functional impact of interface mutations in vitro and in cells.

Outcomes and Impact:

The study will provide a molecular and structural framework for U1-70K–PAP regulation, identify critical residues, reveal complex architecture, and validate biological relevance. Findings will extend beyond virology by expanding understanding of U1 in RNA processing and would enable development of host-directed antivirals targeting RNA maturation steps.

APPLY HERE