Dr Elena Bichenkova is a Reader in Medicinal Chemistry.  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 and Pharmaceutical Sciences as a Research Fellow.  In January 2004 Elena was appointed by the School as a Lecturer in Medicinal Chemistry followed by promotion to Senior Lecturer (2009) and then to Reader (2013).

• 1993 - PhD - Research Institute of Bioorganic Chemistry, Novosibirsk, Russia
• 1983 - M.Sc. equivalent - Research Institute of Bioorganic Chemistry, Novosibirsk, Russia
• 1981 - BSc - Novosibirsk State University, Russia

Pharmaceutical & Medicinal Chemistry aspects within the following teaching units:

• PHAR 10100 'THE MEDICINE' Y1
• PHAR 10102 'PROPERTIES OF MEDICINES' Y1 
• PHAR 20100 'THE MEDICINE' Y2
• PHAR 40100 'THE MEDICINE' Y4
• PHAR 40500 'RESEARCH PROJECT'
• Y4 PHAR41111 'MEDICINES DESIGN AND APPLICATION'

My main research focus is to develop innovative diagnostics and therapeutics through fabrication of functional biomaterials with desired biological properties and controlled functionalities using natural biomacrmolecules (e.g. peptides and nucleic acids) as building blocks. The most important contributions from my research to date include the developments of novel nucleic acid diagnostics and therapeutics to solve biomedical grand challenges, currently unmet by traditional Drug Discovery & Development approaches. 

Molecular diagnostics for potential biomedical and clinical applications

I have previously contributed to the development of small-molecule diagnostic tools for detection of physiological stimuli as potential biomarkers for signalling of tissue abnormalities. Our most recent development includes self-assembling peptidyl-oligonucleotide hydrogels for molecular diagnostics, which offers a 3D sensing capacity and provides a large analyte reservoir thereby enhancing sensitivity and decreasing the detection limits. The controlled self-assembly of individual components into desired 3D nano-architectures is guided by structural biology methods and can be precisely engineered by manipulating the chemical structures of building blocks thus leading to a step-increase in improvement of reliability, accuracy and quality assurance.

Development of novel therapeutic strategies

We have recently developed synthetic catalytic biomaterials capable of recognising and selectively destroying RNA, thus targeting the emerging importance of regulatory RNAs in disease pathways, in order to switch intracellular, paracrine and endocrine signaling pathways from ‘diseased’ to ‘normal’. These advances are particularly beneficial for such biological targets that are not amenable to small-molecule drugs due to the lack of suitable binding sites for small molecules, and also unsuited to large molecule drugs (such as monoclonal antibody inhibition) due to their intracellular location (e.g. transcription factors).

Through our well-established international collaborations, we have recently provided the first experimental evidence that our chemically-engineered peptidyl-oligonucleotide bio-conjugates cleave and silence miR-21 in lymphosarcoma.  Our structural insights into the interactions between these DNA-peptide hybrids and miR-21 will guide future design of such conjugates and accelerate translation of our research outcomes to future therapeutic applications. This discovery of highly-selective bio-mimetics against pathogenic microRNAs over-expressed in disease states opens up a new therapeutic window for drug discovery and provides a world-leading platform to advance development of new therapeutic interventions.

Management/Leadership

SENIOR INTERNAL EXAMINER

For the following  units in the curriculum within the Pharmaceutical & Medicinal Chemistry disciplines (since 2011):

PGR  TUTOR

The role of PGR tutors and advisor (to oversee 32-34 PGR students/year) is to form an oversight network within the School to ensure consistent, reliable assistance, recruitment and supervision of all PGR students in the School (in addition to my roles as an academic supervisor and advisor). PGR tutors are now expected to be involved in individual Skype interviews of each potential PhD applicant.

NMR AND OPTICAL EQUIPMENT

1. Supervision and management of the School’s NMR equipment.
This includes full responsibility for the 300 MHz and 400 MHz spectrometers (Bruker) as well as Pharmacy’s use of the shared 500 MHz spectrometer located in the School of Chemistry, involving:
(i) Supervision of the instruments as well as NMR users (25-30 research users).
(ii) Coordinating training for new NMR users.
(ii) Organisation and management of NMR accounts.
(iv) Spectrometer troubleshooting and routine maintenance (e.g. cryogenic filling on a weekly basis).

2. Supervision and management of the School optical spectroscopy equipment.
Responsibility for the optical spectroscopy facilities (co-applicant BBSRC, Wolfson and EPSRC): two UV-visible, two fluorescence instruments plus 2 x 96-well UV-visible absorption / fluorescence plate reader instruments, FTIR and picosecond lifetime fluorescence. My role includes supervision, maintenance and repair of the instruments and organising training and access for the staff and students users.

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.

TECHNICAL, ADMINISTRATIVE AND MANAGEMENT STAFF

(2013-Current)  Neil O'Hara: Research & Instrumentation Technician (300MHz and 400MHz NMR spectrometers, mass spectrometry facilities, Agilent HPLC instruments and optical equipment  including UV-visible spectrophotometers, fluorescence instruments and 96-well plate reader). 

CURRENT POSTGRADUATE STUDENTS

(2022-2026) Rodion Shipetin: “Development of “smart” nucleic acid therapeutics for future applications against cancer.” Self-funded student, 4 years. (Main supervisor: Dr. Elena Bichenkova; co-supervised by Prof. David J. Clarke).

(2021-2025) Megan Taylor "Selective knockdown of proinflammatory microRNAs to tackle neurodegeneration and cognitive decline: myth or reality?" BBSRC DTP studentship. Main supervisor: Dr Elena Bichenkova. Co-supervisors: Dr Michael Harte  and Prof. Federico Roncaroli.

(2021-2025) Walaa Aburayan "Development of new approaches for anti-cancer therapy: smart, responsive therapeutics against highly oncogenic microRNAs." (Saudi Arabia, sponsored)  Main Supervisor: Dr Elena Bichenkova; Co-Supervisors: Dr Harmesh Aojula and Prof. David Clarke.

(2021-2025) Lina Alaydi "Fostering development of "smart", responsive therapeutics against cancer-related microRNAs" (Saudi Arabia, sponsored). Main Supervisor: Dr Elena Bichenkova; Co-Supervisors: Dr Harmesh Aojula and Prof. David Clarke.

(2021-2024) Chucky Cheung "New approaches for anti-cancer therapeutic interventions: development of "smart" self-sufficient RNA-silencing bioconjugates against highly oncogenic microRNAs." (Hong Cong, self-funded) Main Supervisor: Dr Elena Bichenkova; Co-Supervisor: Prof. David Clarke.

(2021-2024) Fangzhou Shan "New generation of RNA-targeting oligonucleotide analogues as a platform for development of innovative therapeutics against cancer: "smart", responsive bioconjugates against oncogenic microRNAs." (China, self-funded) Main Supervisor: Dr Elena Bichenkova; Co-Supervisor: Prof. David Clarke.

(2020-2024) Niall Mahon "Designing functional 3D scaffolds for cancer early detection" (ACED-funded) Main Supervisor: Prof. Alberto Saiani; Co-Supervisors: Dr Elena Bichenkova and Dr Olga Tsigkou. 

(2018-2023)  Budoor Al Umairi: “Application of Medicinal Chemistry for non-covalent functionalisation of graphene nanomaterials: potential application in screening ‘drug-graphene’ interactions and tracking drug delivery.” Self-funded student, 4 years. (Main supervisor: Dr. Elena Bichenkova; co-supervised by Prof. David J. Clarke).

(2019-2023)    Andrew Irwin: “Fostering the next generation of molecular diagnostics: 3D microfluidic RNA-sensing hydrogel biosensors for clinical analysis of miRNA biomarkers.” BBSRC DTP CASE together with Manchester BIOGEL (Main supervisor: Dr Elena Bichenkova, co-supervised by Prof. Alberto Saiani and Dr Harmesh Aojula; Supervisor at CASE Partner: Prof. Aline Miller).

FORMER POSTGRADUATE STUDENTS

(2018-2022) Thomas Heyman: “Accelerating early-phase development of novel therapeutic interventions: ‘intelligent’ anti-cancer agents against oncogenic microRNAs.” MRC DTP studentship for 3.5 years. (Main supervisor: Dr. Elena Bichenkova; co-supervised by Prof. David J. Clarke and  Dr. Harmesh Aojula).

(2017-2020)  Bahareh Amirloo: “Design and development of novel therapeutic interventions: ‘intelligent’ catalytic systems for irreversible cleavage of disease-relevant RNA.” President’s Doctoral Scholar (PDS) Award with partial self-funding. 2017-2020. Main supervisor: Dr. Elena Bichenkova; co-supervised by Prof. David J. Clarke and Dr. Harmesh Aojula.

(2017-2020)   Sameen Yousaf: “Multi-functional DNA nano-biosensors: self-assembling peptidyl-oligonucleotide hydrogels for potential application in diagnostics and biomedicine”.  The Punjab Educational Endowment Fund (PEEF) with some contribution from President’s Doctoral Scholar (PDS) Award. Main supervisor: Dr. Elena Bichenkova; co-supervised by Prof. Alberto Saian and Prof. Aline Miller.

COLLABORATIONS

Institute of Chemical Biology & Fundamental Medicine (ICBFM; Russia) – International Collaborator

http://www.niboch.nsc.ru/doku.php/en/structure/labs

Well-established collaborative links with ICBFM (through Prof. Marina Zenkova), earlier supported by a Wellcome Trust International Collaborative Award (2001-2004) and by the Russian Science Foundation.

Prof. Tom Brown (FRSC, FRSE), Professor of Nucleic Acid Chemistry at the Departments of Chemistry and Oncology of the University of Oxford

http://www.browngroupnucleicacidsresearch.org.uk/people/view/1/Tom-Brown

Dr. Michela Garofalo, Cancer Research UK Manchester Institute (UoM)

http://www.cruk.manchester.ac.uk/Our-Research/Transcriptional-Networks-in-Lung-Cancer

Prof. David J. Clarke, Director for Anmat Technology Ltd, Old Dutch Barn, Doctor Lane, Scouthead, Oldham, England, OL4 4AD, UK

Dr. Kepa Burusco-Goni, Medicines Discovery Catapult (Alderley Park)

https://www.research.manchester.ac.uk/portal/joanna.neill.html 

Prof. Stuart Allan, Division of Neuroscience & Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health (UoM)

https://www.research.manchester.ac.uk/portal/stuart.allan.html

Prof. Federico Roncaroli, Division of Neuroscience & Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health (UoM)

https://www.research.manchester.ac.uk/portal/federico.roncaroli.html

Prof. Alberto Saiani, Professor of Molecular Materials, School of Materials at the University of Manchester; Manchester Institute of Biotechnology

https://www.research.manchester.ac.uk/portal/A.Saiani.html

Dr. Harmesh Aojula, Division of Pharmacy & Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health  (UoM)

https://www.research.manchester.ac.uk/portal/en/researchers/harmesh-aojula(58f9d413-b44d-446b-8729-04af2b34ce83).html

Dr. Richard Bryce, Division of Pharmacy & Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health  (UoM)

https://www.research.manchester.ac.uk/portal/en/researchers/richard-bryce(a4ad3717-73bf-47d6-9371-e30717522bb3).html