Dr Marco Saponaro

Supervisor Details

Contact Details

Institute of Cancer and Genomic Sciences, University of Birmingham

Scientific Background

Research Interests

Dr Saponaro is interested in characterising mechanisms of genome stability maintenance. In particular he is interested in understanding how RNA Pol II transcription, especially when in mutant contexts that affect transcription progression, can induce genome instability. He develops his research combining whole genome analyses with functional studies. He characterises RNA Pol II progression identifying how it is affected in mutant contexts, correlating transcription problems with the sites of genome instability. All these allow identifying the mechanisms of transcription-induced genome instability.

He is also interested in the relevance for human health of transcription-associated genome instability, identifying instances where these problems arise and approaches to exploit therapeutically these situations.

Scientific Inspiration

He is called Piero Angela, the equivalent of David Attenborough for generations of Italians.

Research Groups

Institute of Cancer and Genomic Sciences

Supervision Style

In three words or phrases: Student-centred; laid-back; supportive.

Provision of Training

As a PhD student in the lab you will be part of a team that includes also postdocs and other PhD students. As such, the training will be provided by a different group member depending on the specific technique/assay.

Progression Monitoring and Management

At the beginning of the PhD we agree in our weekly meetings the goals to reach and it is my responsibility to guide you through the project. When you have acquired enough experience then I’ll be monitoring how you progress with the project.

Communication

The team has a WhatsApp group chat with which we regularly communicate, and my people in my group have my contact details and know that they can contact me at any time for urgent matters or whenever needed.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD study

At least once per fortnight

In year 2 of PhD study

At least once per fortnight

In year 3 of PhD study

At least once per fortnight

The meetings will be face to face and I am usually contactable for an instant response (if required) on every working day.

Working Pattern

Certain tasks in my lab need to occur at set times, and students need to be able to commit to a rota/timetable shared with other members of the team.

Notice Period for Feedback

I need at least 1 week’s notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Primary supervisor for:

Determining how transcription and replication are coordinated during S-phase

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).

Determining how transcription and replication are coordinated during S-phase

Secondary Supervisor(s): Prof Aga Gambus

University of Registration: University of Birmingham

BBSRC Research Themes:

Understanding the Rules of Life (Systems Biology)

Project Outline

RNA Pol II transcription and DNA replication are the two essential processes that use the DNA in our cells as a substrate. However, DNA can be engaged only by one of these processes at any given time, and when transcription impairs DNA replication it can induce DNA damage and genome instability. We have recently shown that transcription activity is transiently reduced to support the replication of genes. We have also identified two separate mechanisms that cells use to regulate transcription activity, depending on when during S-phase transcription and replication meet. Interestingly, one of these occurs only on genes in proximity of the replication fork in early S-phase and alters transcription regulation for several hours. Importantly, both depend on the activity of essential DNA damage checkpoint kinases.

Aims of the project:

We are now interested in investigating into more details how cells regulate transcription activity, using a combination of genome-wide and functional assays:

i) Identifying targets and mechanisms through which cells regulate in a timely manner transcription activity as replication forks progress through the genome.

ii) Determining the consequences for genome stability from the lack of regulation of transcription activity when genes are replicated.

iii) Defining the global impact on transcription activity and chromatin re-establishment if transcription is not properly regulated.

References:

Wang et al., Persistence of RNA transcription during DNA replication delays duplication of transcription start sites until G2/M. Cell Reports 2021

Wang et al., Protocol for analysis of G2/M DNA synthesis in human cells. STAR Protocols 2021

Scaramuzza et al. TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells. Nat Comms 2023

Rojas et al., Genome-wide identification of replication fork stalling/pausing sites and the interplay between RNA Pol II transcription and DNA replication progression. Genome Biology 2024