Author: WISB-Admin

WISB is delighted to announce that Andras Gyrogy, Assistant Professor at NYU Abu Dhabi, will be coming to deliver a talk on Thursday 23rd November. Andras is part of the NetBio Group. Please email wisb@warwick.ac.uk if you would like to attend.

Talk abstract

Without accounting for the limited availability of shared cellular resources, the standard model of gene expression fails to reliably predict experimental data obtained both in vivo and in vitro. To overcome this limitation, we developed a dynamical model of gene expression explicitly modeling competition for scarce resources. In addition to accurately describing the experimental data, this model only depends on a handful of easily identifiable parameters with clear physical interpretation. Based on this model, we characterized the combinations of protein concentrations that are simultaneously realizable with shared resources, matching experimental data both in vitro and in vivo. Application examples of these results include the design of optimal experiments for parts characterization, the characterization of parts whose expression is not accessible through direct measurements, and the standardization of cell-free extracts. Finally, some ongoing efforts will be discussed within the context of biological controller design to address some of the issues caused by the scarcity of shared resources.

Biography

Andras completed his PhD with Domitilla Del Vecchio at MIT (collaborating with Jim Collins and Ron Weiss), during which time he visited Richard Murray at Caltech to work with their TX-TL system. He then spent 1.5 years as a postdoc with Murat Arcak at UC Berkeley (collaborating with Adam Arkin). Currently, he is an Assistant Professor at NYU Abu Dhabi blending wetlab experiments with theoretical analysis on (bio)networks. Building upon the above influences, Andras’s work focuses on network dynamics and synthetic biology (e.g., optimal experiment design, system identification, model order reduction). What he is especially interested in is developing quantitative tools and standardized probes for predicting mRNA and protein expression precisely both in vitro using cell-free extracts and in vivo.

Dr Ozgur Akman is a Senior Lecturer in the Mathematics department at the University of Exeter, and will be visiting WISB as part of our seminar series on Wednesday 8th November.

Ozgur will speak about his research which could lead to the reverse-engineering of large-scale biochemical networks. If you would like to attend, please email wisb@warwick.ac.uk.

The full abstract for Ozgur’s talk is as follows:

The gene networks that comprise the circadian clock modulate biological function across a range of scales, from gene expression to performance and adaptive behaviour. In recent years, computational models of these networks based on differential equations have become useful tools for quantifying the complex regulatory relationships underlying the clock’s oscillatory dynamics. However, optimising the large parameter sets characteristic of these models places intense demands on both computational and experimental resources, limiting the scope of this approach. In this talk, a complementary approach based on combining Boolean logic with evolutionary optimisation will be introduced that dramatically reduces the parametrisation and computational load, making the state and parameter spaces more tractable. Through the construction of Boolean models fitted to both synthetic and experimental time courses, it will be shown that logic models can reproduce the complex responses to environmental inputs generated by more detailed differential equation formulations. In particular, it will be demonstrated that logic models have sufficient predictive power to identify optimal regulatory structures from experimental data. This suggests that the capacity of logic models to provide a computationally efficient representation of system behaviour could facilitate the reverse-engineering of large-scale biochemical networks.

More information on Ozgur’s research. 

Visiting WISB from the DynaMo Center in the Department for Plant and Environmental Sciences at the University of Copenhagen on Wednesday 1st November, Prof Barbara Ann Halkier will be speaking about pathway and transport engineering when using glucosinolates as case study.

If you are interested in attending Barbara’s talk, please email wisb@warwick.ac.uk.

Abstract of Barbara’s talk:

Cruciferous vegetables are unique in synthesizing the natural products glucosinolates. Substantial attention is given to particularly the glucosinolate glucoraphanin that is present in broccoli, as it is generally thought to be the major bioactive compound associated with the cancer-preventive effects of broccoli. The health-promoting effects have resulted in a strong desire to increase the intake of glucoraphanin. Establishment of a microbial production of glucoraphanin will provide a stable, rich source of this compound and enable intake of well-defined doses. Using transient expression in tobacco, we have shown the feasibility of engineering in a heterologous plant the seven genes pathway of indole glucosinolate, and the 12 genes pathway of the glucosinolate glucoraphanin. In yeast and E. coli, we have successfully engineered the benzyl glucosinolate pathways. However, engineering of the 12 genes glucoraphanin pathway poses challenges. Latest development in our goal towards microbial production of glucoraphanin will be discussed. Transport engineering is receiving increased attention as a novel means to control accumulation of specific metabolites. In Brassica crops, glucosinolates are anti-nutritional factors that reduce the nutritional value of the high-quality protein-rich seed meal that is a byproduct in the oil production. Recently, we showed that by mutating two glucosinolate transporters it was possible to eliminate glucosinolates from seeds of the model plant Arabidopsis. As an example of translational biology, we have successfully translated the gtr loss-of-function phenotype from the Arabidopsis model plant to Brassica crops, – a novel and potentially generic transport engineering approach for reducing seed glucosinolate content in other oilseed crops.

Nour-Eldin HH et al. (2017) Reduction of antinutritional glucosinolates in Brassica oilseeds by mutation of genes encoding transporters. Nature Biotechnology, 35, 377

Further information about Barbara’s research can be found here. 

Visiting WISB from the University of Bristol, Dr Ross Anderson will be speaking on Wednesday 11th October at 1pm (MRI room) about the design of new proteins and enzymes and how this remains one of the great challenges in biochemistry.

Ross will explain how our fundamental understanding of both the nature of protein as a material and the principles of enzymatic catalysis is currently being tested and remoulded.

Dr Munehiro Asally will be hosting lunch with Ross beforehand for those interested in speaking with him.

Full details of Ross’s talk can be found in the Seminar Series.