Dr Elena Bichenkova PhD, BSc

Member of School of Pharmacy & Pharmaceutical Sciences Board

Elena’s research is multidisciplinary and primarily concerns nucleic acids chemistry, biochemistry and the study of structural aspects of nucleic acids by high-resolution NMR spectroscopy.  These are synergised with high-level computational approaches and other biophysical methods, including steady state and time-resolved fluorescence spectroscopy.

Working in the DDA group Elena applied her expertise in biophysics and conformational analysis to various areas of medicinal chemistry, biochemistry and molecular biology.  These included study of the structural aspects of processes occurring within nucleic and investigation of molecular mechanisms of ligand-nucleic acid interactions, which were vital elements in structure-based rational drug design.  The success in this area has led on to the discovery of the first examples of synthetic inhibitors of a ribozyme (ribonuclease P, and the first paper related to this discovery has been published in Biochemistry). 

For the last few years Elena has focused her research predominantly on the development of novel approaches for genomic and post-genomic molecular diagnostics, which will provide new generic tools applicable to any nucleic acid detection.

The most recent research of Elena's group is focused on the structural aspects of a new type of artificial ribonucleases with high catalytic turnover and hydrolytic efficiency using high-field 2D NMR spectroscopy and restrained Molecular Dynamics. EPSRC (2006-2009) have supported the investigations of the fundamental processes at the molecular level of these unusual catalytic systems to identify structural rules and molecular mechanisms governing their biochemical activity.

Administration

Supervision and management of the School's NMR equipment
Chair of the School Chemical Safety Sub-Committee
Member of the School Safety Committee
Member of the School Research Committee
Member of the School Promotion Committee

Structural aspects of peptidyl-oligonucleotide chemical ribonucleases

The main focus of our EPSRC funded research was the development of highly specific, synthetic enzymes capable of damaging RNA. The design of novel biocatalytic supramolecular structures mimicking the active centre of natural ribonucleases and capable of cleaving RNA targets can provide a basis for generating new useful biological tools and even powerful therapeutics, affecting specific messenger RNAs and viral genomic RNAs.

In the frame of our collaborative work with Russian colleagues, a new type of chemical ribonucleases with unusual biological and catalytic properties has been developed. These novel compounds were constructed by chemical conjugation of short, synthetic peptides with oligonucleotide fragments. The most remarkable feature of these novel catalytic molecules was that the oligonucleotide mediator enormously enhanced the biological activity of a previously inactive peptide. However, the basic and fundamental processes behind this unusual discovery have never been studied. Therefore, the main focus of our research supported by EPSRC was to provide an understanding at the molecular level of how these functionally significant entities interact with each other and mutually modulate their activities.

The aim of our EPSRC funded research therefore was to determine the structural rules and molecular mechanisms, which govern biological activity of these novel synthetic catalysts and assess whether they can recognize and specifically cleave biologically significant RNA sequences. To achieve this we used various high-resolution NMR structural studies in combination with high-level computational approaches. The results of our research have shown that the merger of two chemical entities (short peptide fragment and synthetic oligonucleotide sequence) seemed to produce a new, hybrid-type of molecule that could synergistically combine the individual properties of the two components to yield a new and unusual biological ability. The oligonucleotide component seemed to induce an `active` structure of the peptide moiety and hence significantly enhance its catalytic performance.

The labelling of these synthetic enzymes with fluorescent tags allowed us to monitor their interactions with RNA sequences, which seemed to be driven by strong non-specific electrostatic interactions and/or by highly specific Watson-Crick hydrogen-bonding. In collaboration with the research groups of David Berk and Alain Pluen (School of Pharmacy) we initiated new studies on evaluation of cellular distribution, transport and trafficking of these compounds using confocal fluorescence correlation microscopy.

• PHAR 40252 Production & Development of Drugs (module co-ordinator)
• PHAR 10101 Organic and Pharmaceutical Chemistry
• PHAR 20091 Pharmaceutical Analysis
• PHAR 20192 Medicinal Chemistry (practicals)

Dr Elena Bichenkova is a Senior Lecturer in Medicinal Chemistry within the Drug Design & Action Group.  Having graduated in Chemistry (BSc - 1983) with a PhD in NMR structural studies of nucleic acids (1993, Novosibirsk, Russia), she continued her research in conformational analysis of biomolecules in the USA at Purdue University (1992, 1994) and then at the University of Texas (1996) collaborating with the first-rank NMR laboratory of Prof. David G. Gorenstein.  After being awarded a prestigious Royal Society/NATO Postdoctoral Fellowship in 1996, she joined the University of Manchester, School of Pharmacy & Pharmaceutical Sciences as a Research Fellow.  In January 2004 Elena was appointed by School of Pharmacy & Pharmaceutical Sciences as a Lecturer in Medicinal Chemistry followed by promotion to the Senior Lecturer level in 2009.

• 1993 - PhD - Research Institute of Bioorganic Chemistry, Novosibirsk, Russia
• 1981 - BSc - Novosibirsk State University, Russia

Collaborators

• Professor Gareth A. Morris
  Chemistry Department, University of Manchester
  - Elena interacts productively not only with the academic groups across the School of Pharmacy, but also with various sectors of the University of Manchester, such as the Department of Chemistry. For a number of years Elena collaborated extensively with Prof. Gareth A. Morris in conformational analysis of biomolecules by high-resolution NMR spectroscopy.
• Drs B. Coe, S. Pope and S. Faulkner
  Chemistry Department, University of Manchester
  - A new project, EPSRC-funded, on novel detector systems follows on from the successful EPSRC pilot project with Dr. Coe.

Affiliated staff

• Professor Ken Douglas
  School of Pharmacy and Pharmaceutical Sciences, University of Manchester
  - For a number of years Elena worked in the Drug Design & Action group, led by Prof. Kenneth T. Douglas. The novel approaches for genomic and post-genomic molecular diagnostics were developed in collaboration with Prof. Ken Douglas.
• Dr Richard Bryce
  School of Pharmacy and Pharmaceutical Sciences, University of Manchester
  - Novel fluorescent dyes for the nucleic acid detection (with LGC, Teddington).
• Dr Julie Andrews
  School of Pharmacy and Pharmaceutical Sciences, University of Manchester
  - Collaborative work on translational regulation of gene expression by human Thymidylate Synthase.