Imperial College London

Krishnan

Faculty of EngineeringDepartment of Chemical Engineering

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 6633j.krishnan

 
 
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Location

 

C503Roderic Hill BuildingSouth Kensington Campus

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Summary

 

Research Overview

The unifying theme of the research in my group is the understanding and manipulation of information processing in cells and tissues. This is approached through a combination of (i) mathematical modelling (ii) theoretical work (iii) systems approaches, including tool development (iv) collaboration with a range of experimentalists. Characteristic of this research area is a  broad diversity of problems at different levels and scales, substantial possibilities for application, and the confluence of the natural sciences, mathematics and engineering, including systems engineering. Some of the approaches developed and employed can be used in related non-biological contexts. This is discussed in greater detail below.

 

The regulation of most aspects of cellular life and functioning is accomplished by complex and sophisticated biochemical and gene regulatory networks (the intracellular level) along with cellular communication and interaction (the tissue or cell population level). The functioning of such networks both at intracellular and the intercellular level  is being probed in a broad diversity of settings. Understanding the functioning of and information processing through  these  networks is of central importance both from basic and applied perspectives. This is because it allows us to understand how cells regulate different processesand respond to the environment and affords ways of controlling or manipulating them through synthetic and other means.

        There are a broad range of challenges involved in this endeavour. The complexity of information processing in cells and tissues stems from multiple sources. In addition to the large number of molecular components, abundant nonlinearity in different forms, widespread feedback, the effects of stochasticity and spatial aspects and the different forms of cellular interaction all play important roles. Furthermore, the organization of networks, shaped by evolution, is subtle. Dissecting the behaviour of cells and tissues and information processing through them involves the confluence of biology, physics, chemistry, mathematics and engineering. Engineering approaches are involved both in the understanding and manipulation of cellular networks

    The research in my group employs an interdisciplinary engineering approach in this context, with two broad strands. The first strand involves mathematical and computational modelling in a selection of concrete problems of basic and applied interest. We collaborate with cell biologists, biomedical scientists and engineers as well as synthetic biologists in this regard. Mathematical modelling involves temporal, spatial and stochastic descriptions as appropriate and some of the modelling is explicitly multi-level. We develop both simplified and detailed mechanistic models which are analyzed through computational and analytical means.

A complementary strand of research involves developing theoretical and systems frameworks and tools to elucidate different aspects of signal transduction, gene regulation and information processing. The  goals here include the elucidation of different aspects of signal transduction, gene regulation and information processing and the creation of platforms and tools which may be relevant in multiple contexts/systems. These approaches are relevant to both systems and synthetic biology, as they help build a bridge to tackle the complexity of natural systems on one hand, and serve as a foundational platform for engineering them on the other. Tools from dynamical systems, control engineering, systems engineering and networks are employed here.

 The research of each strand informs the other, and employing both approaches allows for a synergistic interplay between the two.

Recent and ongoing research focusses on a range of problems across different levels and scales including (i) Modelling and analysis of information processing in complex enzymatic mechanisms such as multisite phosphorylation (ii) mRNA translation: feedback regulation, the effects of premature stop codons, and the interplay between recycle and mRNA stability (in collaboration with Prof. Ian Stansfield), tools for modelling and analysis of mRNA translation. (iii) The regulation of cell cycle control system in dynamic environments (iv) Different aspects of information processing in signal transduction and gene regulatory modules and networks (v) The spatial regulation of signal transduction and information processing (vi) Elucidating effects of different drug resistance mechanisms in tumours at cell and tissue levels (partly in collaboration with Rongjun Chen) (vii) Engineering spatial regulation and patterns at the intracellular and tissue levels (collaboration with multiple colleagues at Imperial College, including Oscar Ces and Mark Isalan).

Finally, we are also interested in non-biological analouges and extensions of different aspects of the above research, as well as dynamics and self-organization in engineered and related physicochemical systems.

 

Funding: BBSRC,EPSRC

Former Group members: Yun-Bo Zhao (Postdoc: currently faculty member at Zhejiang University of Technology), Eric de Silva (Postdoc: currently at IBME, University College London), Cong Liu (PhD, currently postdoc with Prof. Stephen Smith, University of Oxford), Daniel Seaton (PhD, currently postdoc with Prof. Andrew Millar, University of Edinburgh), Oleg Lenive (PhD cosupervised with Prof. Michael Stumpf), Kristina Mois (MSc), Chonlatep Usaku (MSc), Nemanja Mikac (MSc), Nuri Purswani (MSc:bioinformatics),Ioannis Floros (MSc), Marc Kaloustian (MSc). Marie Uppiah (UG), Anni Tao (UG), Harkamaljot Kandail (UG), Weng Chang (UG), Priyank Shah (UG)

Current members: Aiman Alam-Nazki, Thapanar Suwanmajo, Govind Menon, Junjun Cai, Manfredi San Germano, Luis Manriquez, Richard Amaee, Shayne Petkiewicz, Jisiyuan Chang, Faraz Kavahei,Chinedu Okeke

 

Recent News:

Aiman Alam-Nazki won the Dudley Newitt Prize for Theoretical and Computational Excellence in the Department of Chemical Engineering (2016)

Yun Bo Zhao was selected in the 1000 Plan Program for young talents, Government of China (2015)

Aiman Alam-Nazki was awarded an EPSRC Prize Fellowship (2015)

Thapanar Suwanmajo won a Highly Commended Award in the category of Engineering (one winner and one highly commended award is given in the category of engineering), in the Anglo-Thai Society Educational Awards for Excellence (2014)