Biological Sciences

Profile

BSc, PhD, MIoN, ILTM

Dr Firman has studied Type I Restriction-Modification enzymes for >25 years, investigating both protein-protein interactions and protein-DNA interactions. The interest in these enzymes has recently been spurred by a series of single molecule studies, in collaboration with a number of European Partners, that have described the detailed assembly and molecular motor function of these complex multifunctional enzymes. This work has recently led to the concept that these molecular motors can form the basis of single molecule devices and we believe this work could spearhead commercial development of bionanotechnology.

Recent Collaborations

Two recent European Projects (Mol Switch and BioNano-Switch) have involved partners from the following organisations:

• The National Physical Laboratory, Teddington, UK.
• The Technology University of Delft, The Netherlands.
• Ecole Normale Superieure, Paris, France.
• The Institute of Microbiology, The Czech Academy of Sciences, Prague, Czech Republic.
• The University of Parma, Parma, Italy.
• EMPA, Thun, Switzerland.
• INESC-MN, Lisbon, Portugal.

Previous international collaborations have involved groups from Tel Aviv University, IMG, Moscow and the University of Birmingham, Alabama. While recent UK-based collaborations have involved The University of Edinburgh and the University of Bristol.

Research Interests

• Coordinator of NanoNet Network. This Network runs regular workshops on Bionanotechnology and seeks to establish new collaborations in Bionanotechnology. We are looking at ways to expand the membership with industrial partners. The Workshops have all been video-recorded and the video streams are available to NanoNet Network members.
• Development of Molecular Machines, Self-Assembling Nanodevices and Bionanotechnology. We are seeking commercial routes to exploit technology developed around the use of biological molecular machines. This includes single-molecule biosensing, "personalised" gene-drug interactions and intelligent materials.
• Synthetic Biology and Surface Engineering - self-assembly biosystems on surfaces, applied research approaches to production of nanodevices from existing recombinant systems. Cassette-type construction of biological production systems and their incorporation into purpose designed nanodevices.
• Type I Restriction and Modification Systems.
• DNA methylation.
• DNA modification.
• Gene cloning.
• PCR fingerprinting.
• Genetic engineering.
• Molecular biology.

Teaching Interests

• Genetic engineering
• Molecular biology
• Genomics and Protemics
• Bionanotechnology
• Communication in science

Commercialisation Activities

Dr Firman was recently awarded the status of a CommercialiSE Fellow (this involved a 6-day workshop to introduce commercial terminology, business law and production of a Business Plan). This Fellowship is supported by Finance SouthEast, who also provided SePOC (Proof of Concept funding - detailed below), which has allowed us to demonstrate the capabilities of the molecular motor for detection of toxic materials.

This work has led to industrial collaborations with Cybersense Biosystems Limited, who are world leaders in rapid toxicity testing of reclaimed and "brown field sites" and Farfield Scientific Limited, who are world leaders in development of sensors for nanotechnology.

The University is now considering the concept of a spin-out company to develop the technology involving the molecular motor as a Lab-on-a-Chip device for a broad range of biosensing applications. The motor will form the active part of a single-molecule molecular dynamo, which provides a electromagnetic transducer outputting an electronic signal from a biological input.

Current Research Grants

A Biological Nanoactuator as a Molecular Switch for Biosensing, NEST Pathfinder (Synthetic Biology), EC grant, €1,992,610.

A self-assembling multisubunit biosensor for toxicity testing. SePOC, £49,020

NETWORK: Molecular machines in nanotechnology, EPSRC, £63,053

A Molecular Magnetic Switch that links the Biological and Silicon Worlds, FET-OPEN EU grant under IST, €1,974,000

"Trojan Horse" - nano-scale packaging, separation and delivery device, Wellcome Trust Showcase Award (with Darek Gorecki - Principal Investigator), £125,000.

Recent Publications

Youell, J., and K. Firman. (2007). Biological molecular motors for nanodevices. Nanotechnology Perceptions 3: In press.

Obarska, A., Blundell, A., Feder, M., Vejsadová, T., Šišáková, E., Weiserová, M., Bujnicki, J.M., and Firman, K. (2006) Structural Model for the Multisubunit Type IC Restriction-Modification DNA Methyltransferase M.EcoR124I in complex with DNA. Nucl. Acids Res. 34:1992-2005.

Seidel, R., Bloom, J.G.P., van Noort, J., Dutta, C.F., Dekker, N.H., Firman, K., Szczelkun, M.D., and Dekker, C. (2005) Dynamics of initiation, termination and reinitiation of DNA translocation by the motor protein EcoR124I. European Molecular Biology Organisation Journal 24: 4188-4197.

Firman, K. (2005) A Molecular Magnetic Switch that links the Biological and Silicon Worlds. In IST-FET Newsletter. Vol. 1, pp. 4.

van Noort, J., van der Heijden, T., Dutta, C.F., Firman, K., and Dekker, C. (2004) Initiation of Translocation by Type I Restriction-Modification Enzymes is Associated with a Short DNA Extrusion. N.A.R. 32: 6540-6547.

Holubova, I., V. Stepánka, K. Firman, and M. Weiserova. 2004. Cellular Localization of Type I Restriction-Modification Enzymes is Family Dependent. Biochemical and Biophysical Research Communications 319:375-380.

Pennadam, S., M. D. Lavigne, C. F. Dutta, K. Firman, D. Mernagh, D. C. Górecki, and A. Cameron. 2004. Control of A Multi-Subunit DNA Motor By A Thermo Responsive Polymer Switch. Journal of the American Chemical Society Accepted subject to revision.

Pennadam, S. S., K. Firman, C. Alexander, and D. C. Górecki. 2004. Protein-polymer nano machines. Towards synthetic control of biological processes. Journal of Nanobiotechnology 2:1-7.

Seidel, R., J. van Noort, C. van der Scheer, J. G. P. Bloom, N. H. Dekker, C. F. Dutta, A. Blundell, T. Robinson, K. Firman, and C. Dekker. 2004. Real-Time Observation of DNA Translocation by the Type I Restriction-Modification Enzyme EcoR124I. Nature Structural Biology 11:838 - 843.

Abadjieva, A., et al., Characterisation of an EcoR124I DNA Restriction-Modification Enzyme Produced from a Deleted Form of the DNA-Binding Subunit, Which Results in a Novel DNA Specificity. Folia Microbiol., 2003. 48(3): p. 319-328.

Roberts, R. J., M. Belfort, et al. (2003). "A nomenclature for restriction enzymes, DNA methyltransferases, homing endonucleases and their genes." Nucl. Acids. Res. 31(7): 1805-1812.

Firman, K. and C. F. Dutta (2001). Restriction-Modification Endonuclease Sub-Unit Protein. Europe patent number 01309502.

Firman, K., C. Dutta, et al. (2000). "The role of subunit assembly in the functional control of type I restriction-modification enzymes." Molecular Biology Today 1(2): 1-8.

Firman, K. and M. Szczelkun (2000). "Measuring motion on DNA by the type I restriction endonuclease EcoR124I using triplex dissociation." European Molecular Biology Organisation Journal 19(9): 2094-2102.

Holubová, I., S. Vejsadová, et al. (2000). "Localisation of the type I restriction-modification enzyme EcoKI in the bacterial cell." Biochemical and Biophysical Research Communications 270: 46-51.

Janscák, P., M. Weiserová, et al. (2000). "Two temperature-sensitive mutations in the DNA-binding subunit of EcoKI with differing properties." FEMS Microbiol. Lett. 182: 99-104.

Lisle, W., C. F. Dutta, et al. (2000). "Phage T4-encoded Stp alleviates the DNA restriction activity of EcoR124I endonuclease by affecting a critical step in the subunit assembly pathway." Molecular Biology Today 1(2): 57-64.

Weiserova, M., C. F. Dutta, et al. (2000). "A novel mutant of the type I restriction-modification enzyme EcoR124I is altered at a key stage in the subunit assembly pathway." Journal of Molecular Biology 304(3): 301-310.

Firman, K. (1999). A polynucleotide motor. United Kingdom, WO 00/71681.