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Quantifying global burden and contextual effects of synthetic genetic circuits in their bacterial chassis
Lead Research Organisation: University of Cambridge
Department Name: Engineering
Synthetic biology uses standardised biological parts, formed from engineered DNA sequences, which can be combined to form devices and systems which perform useful functions. The combination of parts necessary for a given function is called a synthetic genetic circuit, and when a circuit is placed inside a host bacterium the circuit DNA is expressed by the cellular machinery of the host. Potential uses for synthetic biology include applications in agriculture, healthcare, environmental remediation, biosensing and sustainable manufacturing.
However, the expression of synthetic circuit DNA uses a portion of the limited resources available to the host cell for cell growth and reproduction. Therefore, circuit containing cells typically have a lower growth rate and organism fitness than their circuit free counterparts. We refer to this general slow-down of cellular activity due to resource competition as a global burden on the cell. The expression or maintenance of the circuit can also inhibit the natural function of specific genes in the host genome, which can be detrimental to organism fitness, but can also feedback and impair the circuit function itself.
Therefore, the general resource competition from the parasitic nature of the circuit, and context dependent interactions between the circuit and its host can reduce both the performance quality of the circuit and the fitness of the host. These pose major problems for engineering synthetic circuits, since in addition to reducing yields, the reduced organism fitness creates a selective pressure against the circuit containing cells, meaning they are likely to be outcompeted by any cells which mutate to lose the circuit and hence reduce the burden they experience. In general, this means useful functions performed by circuits are very quickly lost from a population of cells.
In this project, we aim to precisely quantify the global burden and the contextual effects arising from a synthetic circuit, and to characterise any loss in circuit performance and evolutionary robustness due to these effects. To achieve this, we will use time-lapse microscopy to image live cells growing in a high-throughput microfluidic chamber where cells will grow in a uniform environment, with single cell resolution. By inducing a controlled circuit loss, we will be able to precisely measure the difference in growth rates between genetically identical cells containing and free from the circuit.
Furthermore, through long term observation of mutations in the circuit and host genome, we aim to gain insight into how cells evolve to co-exist with a synthetic circuit. We aim to achieve this using a custom built, automated growth chamber which controls the optical density of the bacterial culture. We believe this methodology will allow us to observe many more generations per unit time over the length of the experiment than traditional long-term evolution experiments. Through regular DNA sequencing of samples from these evolution experiments, we will be able to quantify the rate and manner by which circuit function is lost.
Lastly, we aim to introduce a synthetic circuit into collections of bacterial strains, where each strain tracks the activity of a different gene in the bacterial genome. By inducing a controlled circuit loss from these strains, and observing the activity of each gene in the genome both with and without the circuit, we hope to deduce whether and how the operation of the synthetic circuit inhibits the expression of others genes of the organism.
This project most closely aligns with the Synthetic Biology EPSRC research area, and a key outcome of this project could be to provide quantitative, metrological benchmarks and new methods for the measurement of burden in bacterial cells. The project also aligns with the Sensors and Instrumentation research area, due to the focus on developing new and precise methods for measuring burden and contextual effects caused by synthetic genetic circuits.
Charles David Wedd
University of Cambridge, United Kingdom (Lead Research Organisation)
Somenath BAKSHI (Primary Supervisor) http://orcid.org/0000-0003-3864-2546
Charles David Wedd (Student)
EP/S023046/1 01/10/2019 31/03/2028
2262510 Studentship EP/S023046/1 01/10/2019 30/09/2023 Charles David Wedd


AfL Seminar: Is it really Albert's Hall? How one woman's determination shaped the evolution of the arts and sciences in South Kensington.
Prince Albert is forever connected to the great hall in South Kensington that bears his name, and has long been seen as the iconic symbol of Albert's work for the arts and sciences. However, it seems that the great hall was conceived after his death by Queen Victoria, their son Bertie, and the entrepreneur Henry Cole. This seminar will therefore discuss the 'real' story behind Albert's Hall. Beginning with his work for the Great Exhibition, we will turn to how Queen Victoria chose to celebrate and continue Albert's legacy after his death in 1861. This seminar will include an examination of documents from a number of archives, including letters in Albert's own hand, and examples of music which were performed during the Hall's early years.
Fiona Gibbs graduated from the Royal College of Music in 2018 with a doctorate in Music. She is hoping to publish her thesis, 'The Royal Albert Hall: A Case Study of an Evolving Cultural Venue' in the near future. Fiona has previously spoken for Archives for London in 2014 and at the BBC Proms, the Royal Musical Association, Imperial College, Ted Talks and the Foundation for International Education. A professional violinist, Fiona performs regularly on a freelance basis and she is part of several chamber ensembles and orchestras, including The Gibbs Trio, with her brothers. In 2012 Fiona co-founded 'Orchestra Vitae', which provides musical workshops for schoolchildren in London.
Alongside her academic and performance work, Fiona teaches violin, piano and music theory.
Advance booking is essential. Please book your place through Eventbrite or by telephoning Alex Fisher (AfL Secretary) on 020 7594 8818.
This talk will consider the history of the Turner Bequest at the National Gallery, starting by looking at Turner's will, how it was contested by his relatives before the Court of Chancery, and the resolution of the court case. We will then turn to the history of the display of the Turners at Trafalgar Square and the complicated relationship between the National and Tate Galleries as they sought to determine the final, and at times controversial, distribution of the bequest.
Alan Crookham is Research Centre Manager at the National Gallery where he is responsible for the management of the library and archive collections and for the strategic development of both physical and digital access to these resources and augmentation of their use for research. He also works to support collaborative research activities both within the Gallery and with the broader academic community. Alan is the author of The National Gallery: An Illustrated History.
27th March – Is it really Albert's Hall? How one woman's determination shaped the evolution of the arts and sciences in South Kensington.
6th December – Archives of the Worshipful Company of Musicians.
23rd January – From Big Ben to the Liberty Bell: the archives of Whitechapel Bell Foundry.
27th February – Alderman Arnold fitz Thedmar – London's first civic historian.
We run workshops for professional archivists and archives users based on the needs of our membership. While we have none currently planned, we would like to hear from you if you have a particular skill or topic you would like to see covered. You can contact us here.


Apple's event is on 12 September at the door. A little surprise seems to be gone because with 9to5Mac one wants to have come to official pictures of the coming iPhones. These will be available in sizes of 5.8 and 6.5 inches. Both devices come with an OLED display. One is not sure, but believe that the new iPhone 2018 will be marketed under the name iPhone XS. Further details are not yet known, except that the smartphone should also be offered in the color gold. Apple is expected to introduce the new Apple Watch Series 4 at the same event.