Schools Partnership Researching Chromosome Stability

Pupils at schools in Sussex are supporting genome researcher Dr Jon Baxter through an innovative citizen science project.

Research in the Baxter lab is focussed on understanding the mechanisms and regulations that drive the duplication of the DNA (‘DNA replication’) and what happens if these processes go wrong. Although the ultimate goal is to understand how human diseases develop, the lab uses the simpler baker’s yeast (Saccharomyces cerevisiae), which has similar biological processes to human cells.

Dr Baxter established the University of Sussex School Partnership Researching Chromosome Stability – SPaRCS as a program to involve Yr12 and Yr 13 students in conducting chromosome stability experiments for live research projects. For the project, students grow yeast with different modifications in genes that are known, or suspected, to play a role in maintaining genetic stability. Using a classical yeast genetic assay, 'colony sectoring', students assess if these mutations lead to chromosomal instability. This assay is visual, non-toxic and easy to carry out in a school environment.

The pupils identify which genetic modifications result in increased DNA instability, and their data is fed back to the university for further investigation.

SPaRCS is enabling students to be involved in current research, developing their skills in laboratory techniques, teamwork and problem solving, while increasing their awareness of scientific research.

Please see the tabs below for more information on the project. If you would like to find out more, please contact the Public Engagement Coordinator, k.petherick@sussex.ac.uk.

Project History

SPaRCS has been growing since October 2016, when we worked with Gildredge House Free School in Eastbourne as part of a Royal Society Partnership Grant. It was a fantastic collaboration where the students got stuck into the project, and we learnt what does and doesn’t work in a school lab setting!

The following year we worked with Brighton and Hove High School (BHHS) and Brighton, Hove and Sussex Sixth Form College (BHASVIC), where we ran a similar programme to the one with Gildredge House, along with adding another dimension – counting via Zooniverse; you’ll hear more about that later in the book. It was great to see how different schools approached the project and to understand what best support we can provide.

Now in its third year, we are working with undergraduates to act as mentors for students, as well as introducing better instructions and support mechanisms, including a lab book and instruction video.

Scientific Background

Trillions of cell divisions are necessary to form a human body from a zygote (fertilised egg cell). Even in the adult body billions of new cells are produced by cell division. These cells need to faithfully copy their genetic material during each multiplication. Gain, loss or alteration of the DNA might lead to developmental diseases, cancer or aging. So it is extremely important to understand how cells copy their DNA, and once it is replicated how they divide the two copies equally into the new offspring cells.

Although the ultimate goal is to understand how human diseases develop and how we can prevent or cure them, it is still very laborious and in most cases impossible to directly study certain mechanisms in human cells. Luckily the core processes of DNA replication in simpler, single cell organisms are very similar to that of humans. Baker’s yeast (Saccharomyces cerevisiae) has already helped scientists to gain insight to several biological processes that turned out to be the same in human cells. Yeast is much easier to grow in culture and takes much less effort to be genetically modified than human cells. For these reasons we use yeast as our model organism.

DNA in living cells is usually divided into smaller chunks, called chromosomes. After DNA replication there are two copies of each chromosome in the cell and one copy of each has to be directed to both offspring cells. Defects in the copying system can lead to changes in parts of the chromosomes, and faults in the mechanism that separates the chromosomes could lead to unequal distribution between the new cells. That means that one of the cell will lose or gain one or more chromosomes or parts of a chromosome (this is called aneuploidy).

To study what changes within the copying or separating apparatus result in alterations in the genome we introduce a small artificial chromosome (‘mini-chromosome’) in our yeast strains. The presence of this mini-chromosome is not essential for the yeast, they can grow and form colonies without it. However the mini-chromosome contains a gene which makes the colour of the colonies red. If the chromosome and its colour gene are lost due to defective DNA replication, the cells go white.

This allows us to follow when the cells lose the mini-chromosome just by looking at the colour of the colony. The faster the yeast cells lose the red colour, the less stable the genome is. Counting colonies with different patterns shows us how often cells lose their mini-chromosome. This is termed a ‘colony sectoring assay’.

We can change or delete the genes of specific proteins that we know, or suspect, to play a role in maintaining genetic stability. The colony sectoring assay will then assess whether these proteins are needed to keep the chromosomes intact and what specific alterations (‘mutations’) in these proteins lead to genetic instability. Our results than can guide further studies in human cells to better understand processes in e.g. cancer and aging.

At present our research is focusing on an evolutionary conserved protein called Timeless in humans and Tof1 in yeast. Tof1/Timeless appear to have a role during DNA replication in maintaining genome stability, but the molecular nature of this function is unknown. We have already changed several parts of this protein in our system and have found that loss of Tof1 function leads to frequent loss of the mini-chromosome. We now want to see which specific changes to the Tof1 gene changes the protein enough to lead to genome instability (measured by loss of the mini-chromosome and colour change). This will inform us which parts of the protein are important for its function and how it interacts with other proteins.

We provide schools with a variety of yeast strains that have different mutations in the TOF1 gene, and the students carry out the colony sectoring assay on these different strains, to help us understand which (if any) of these mutations affect chromosome stability compared to the normal (wild-type) gene. These results are unknown, so the students are contributing directly to our ongoing research.

Results so far

Work in several schools has shown that while a shortened (’truncated’) Tof1 protein that contains the first 80% of itself (tof1-997) can mostly maintain the Tof1 function in chromosome stability, a Tof1 protein containing just the first 75% of the protein (tof1-901) cannot (see Figure below).

These data suggest that the structure of the protein in this region (901-997) is crucial for Tof1 to normally function. We will next be investigating a series of other mutations that are focused in and around this area to both confirm and extend these initial findings. Remember, we don’t know what the results will be, so you’ll be the first people in the world to find out!

Why get involved?

The students at Brighton and Hove High School said: “Our research will contribute to a larger project undertaken by the University of Sussex. Through this experiment we have been able to study the effect of genetic modification on cells of various forms and through this, exploring mutation and the nature of it. In the future our research could contribute to a wider project of cancer research and provide large amounts of information on how tumours grow and spread as quickly as they do, and ways in which we can fight and control them in the least invasive or damaging way possible. Hopefully, our data will enable scientists to gain a clearer understanding and help them make decisions. Our data will help the university identify which strain to focus the more expensive techniques on, thus saving the university time and money.

“Our main goal was to successfully carry out the whole process and get valid and helpful data that we could give back to the university and help them in their research. We wanted to prove that it is possible for schools to be able to work with universities and people working in science, to collaborate and benefit the learning of the pupils and also help carry out easy experiments that would create data vital towards other studies. This would allow our project to be done on a more national scale and could help future research projects speed up the lengthy process. We also wanted to produce this document, to help other schools with the setting up process that took us such a long time.” 

One student from Gildredge House gained one of a very limited number of places on an apprenticeship training course to become a university biology laboratory technician. Her teacher said: “Her participation in the project ignited an interest in laboratory work and the experience and skills she gained from being a part of the project allowed her to stand out in the application process."

Link to curriculum

Participation in SPaRCS develops 9 of the 11 stated aims of the subject content of biology A level  and specifically builds on core concept 5 of the A level curricula as well as training teachers in research and genetics.

Academic curriculum
Develop and demonstrate appreciation of the skills, knowledge and understanding of scientific methods used within biology.
Develop competence and confidence in a variety of practical, mathematical and problem solving skills.
Carry out experimental and investigative activities, including appropriate risk management, in a range of contexts.
Evaluate methodology, evidence and data, and resolve conflicting evidence.
Demonstrate and apply knowledge and understanding of: DNA, genes and protein synthesis; DNA replication and mitosis; genetic diversity; control of gene expression.

Personal development
Teamwork; troubleshooting; critical thinking; timekeeping.
Careers and higher education links:
Linking curriculum learning to careers.
Experiences of workplaces.
Encounters with further and higher education.

Lab book

Download the Lab Book here.

Instruction video