Overview
Dr Erum joined the University of Exeter Medical School in 2020. She obtained her PhD from the University of Central Lancashire in discovering antimicrobial peptides and their mechanism of action against pathogenic bacteria. Dr Erum also got her Master’s degree in Biomedical Engineering and in Biochemistry. Her subject areas are biochemistry, cell and molecular biology and genetics.
Currently, Dr Erum is a Lead for Technology Enhanced Learning (CMH). She repreprents CMH for the AV enhancement facility for hybrid teaching.
Qualifications
- Postgraduate Certificate in Academic Practice (University of Exeter)
- Fellowship of the Higher Education Academy, AdvanceHE, UK
- PhD Antimicrobial peptides (University of Central Lancashire)
- MSc Biomedical Engineering (University of Bedfordshire)
- MSc Biochemistry (SALU, Pakistan)
Career
Before moving to the UK, Dr Erum was trained in Biochemistry and has started her career as a lecturer at Shah Abdul Latif University, Pakistan. In 2011, She moved to the UK where she obtained Masters in Biomedical Engineering from the University of Bedfordshire. Then, Dr Erum went to the University of Central Lancashire where she got PhD in discovering the mode of action of antimicrobial peptides.
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Research
Research interests
Dr Erum’s research interest lies in discovering new antimicrobial agents. Antimicrobial resistance is a major health problem throughout the world and antimicrobial peptides provide a promising alternative strategy to this health problem. Dr Erum investigated the pre-clinical drug potency of the peptides, their interaction with the membrane of host cells (cancerous & bacterial cells), the structure and function relationship, protein conformation, folding and mechanism of action of the peptide in different pH environments using microbiology, biochemistry, biophysical and computational techniques.
Research Papers:
- Erum Malik, David A. Phoenix, Timothy J. Snape, Frederick Harris, Jaipaul Singh, Leslie H.G. Morton, Sarah R Dennison. (2021). Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum. Molecular and Cellular Biochemistry. 10.1007/s11010-021-04181-7
- Mubashir Hassan, Sara Zahid, Saba Shahzadi, Erum Malik, Sumera Zaib, Jamshed Iqbal, Saba Shamim, Arif Malik. (2020). Mechanistic Insight of DACH1 receptor in the development of carcinoma insurgence through MD simulation studies. Journal of Biomolecular Structure & Dynamics. doi.org/10.1080/07391102.2020.1818624
- Wasim Ahmed, Muhammad Bilal, Amir Hayat, Muhammad Umair, Asmat Ullah, Sundus Khawaja, Erum Malik, Nousheen Gul, Umm-e- Kalsoom, Sulman Basit. (2020). Sequence variants in the WNT10B and TP63 underlying isolated split hand-split foot malformation. Genetic Testing and Molecular Biomarkers. doi.org/10.1089/gtmb.2020.0024
- Erum Malik, David A Phoenix, Kamal Badiani, Timothy J Snape, Jaipaul Singh, Frederick Harris, Sarah R Dennison. (2020). Biophysical studies on the antimicrobial activity of linearized esculentin 2EM. BBA – Biomembranes. https://doi.org/10.1016/j.bbamem.2019.183141
- Muhammad Umair, Amjad Khan, Safder Abbas, Farooq Ahmed, Muhammad Younus, Wajid Amin, Shoaib Nawaz, Amir Hayat, Erum Malik and Majid Alfadhel. (2019). Biallelic missense mutation in the ecel1 underlies distal arthrogryposis Type 5 (DA5D). Front. Pediatr. DOI: 10.3389/fped.2019.00343
- Muhammad Younus, Farooq Ahmed, Erum Malik et al. (2019). SGCD Homozygous Nonsense Mutation (p.Arg97∗) Causing Limb-Girdle Muscular Dystrophy Type 2F (LGMD2F) in a consanguineous family, a Case Report. Front. Genet. doi.org/10.3389/fgene.2018.00727
- Erum Malik, Sarah R. Dennison, Frederick Harris and David A. Phoenix. (2016). pH-dependent antimicrobial peptides and proteins, their mechanisms of action and potential as therapeutic agents. Pharmaceuticals. DOI: 10.3390/ph9040067
SCIENTIFIC CONFERENCES AND MEETINGS
Poster Presentations
• Erum Erum and Wondwossen Abate. "Pictorial vs Text-based feedback in LSRC sessions in Medical Education". (2023). School of Education student-staff Research Conference, Univeristy of Exeter.
• Wondwossen Abate and Erum Erum. "Interprofessional learning through problem-based learning: oppertunities and challenges". (2023). School of Education student-staff Research Conference, Univeristy of Exeter.
• Erum Malik, Sarah R. Dennison, Frederick Harris, Jaipaul Singh and David A. Phoenix, International Meeting on Antimicrobial peptides (2018), Edinburgh.
• Erum Malik, Sarah R. Dennison, Frederick Harris, Jaipaul Singh and David A. Phoenix, International Meeting on Antimicrobial peptides (2015), London.
• Erum Malik, Sarah R. Dennison, Frederick Harris and David A. Phoenix, 4th Annual Research Student conference (2014), University of Central Lancashire.
• Erum Malik, Sarah R. Dennison, Frederick Harris, Jaipaul Singh and David A. Phoenix, Circular Dichroism Annual Meeting (2014), University of Warwick.
• Erum Malik, Poster Competition, Department of Biomedical Engineering, (2012), University of
Bedfordshire.
Oral Presentations
• Erum Malik, 3 Minute Thesis presentation (2017), University of Central Lancashire.
• Erum Malik, Sarah R. Dennison, Frederick Harris and David A. Phoenix. The Post Graduate
Research Forum (2014), University of Central Lancashire.
• Erum Malik, Group meeting, School of Pharmacy and Biomedical Sciences (2013), University of
Central Lancashire.
• Erum Malik, Department of Biomedical Engineering, (2012), University of Bedfordshire.
• Erum Malik, World Environment Day (2010), SALU, Pakistan
• Erum Malik, 1st National Training Course on Biochemical Techniques (2008), SALU, Pakistan
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Publications
Journal articles
Hassan M, Zahid S, Shahzadi S, Malik E, Zaib S, Iqbal J, Shamim S, Malik A (2022). Mechanistic insight of DACH1 receptor in the development of carcinoma insurgence through MD simulation studies.
J Biomol Struct Dyn,
40(2), 742-751.
Abstract:
Mechanistic insight of DACH1 receptor in the development of carcinoma insurgence through MD simulation studies.
Proteins are key player in the prognosis and therapeutics of carcinomas through the interactions of downstream signalling cascades. Current work insight the structural and mutational analysis of DACH1 in association with carcinogenesis. The homology modelling was employed to predict mutant and wild protein models and their reliability and accuracy was verified through multiple online approaches. Furthermore, MD simulation technique was employed to check the mutation effects on the stability of DACH1 through root mean square deviation and fluctuation graphs. Our results proposed that DACH1 mutation (C188Y) may cause lethal effects and can disturb the DACH1 structure. The observed mutational results showed that C188Y may cause some lethal effect in human body. Based on aforementioned computational assessments, it has concluded that DACH1 could be used as good therapeutic target in the prognosis and therapeutic of carcinoma insurgence.Communicated by Ramaswamy H. Sarma.
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Malik E, Phoenix DA, Snape TJ, Harris F, Singh J, Morton LHG, Dennison SR (2021). Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum.
Mol Cell Biochem,
476(10), 3729-3744.
Abstract:
Linearized esculentin-2EM shows pH dependent antibacterial activity with an alkaline optimum.
Here the hypothesis that linearized esculentin 2EM (E2EM-lin) from Glandirana emeljanovi possesses pH dependent activity is investigated. The peptide showed weak activity against Gram-negative bacteria (MLCs ≥ 75.0 μM) but potent efficacy towards Gram-positive bacteria (MLCs ≤ 6.25 μM). E2EM-lin adopted an α-helical structure in the presence of bacterial membranes that increased as pH was increased from 6 to 8 (↑ 15.5-26.9%), whilst similar increases in pH enhanced the ability of the peptide to penetrate (↑ 2.3-5.1 mN m-1) and lyse (↑ 15.1-32.5%) these membranes. Theoretical analysis predicted that this membranolytic mechanism involved a tilted segment, that increased along the α-helical long axis of E2EM-lin (1-23) in the N → C direction, with - increasing overall from circa - 0.8 to - 0.3. In combination, these data showed that E2EM-lin killed bacteria via novel mechanisms that were enhanced by alkaline conditions and involved the formation of tilted and membranolytic, α-helical structure. The preference of E2EM-lin for Gram-positive bacteria over Gram-negative organisms was primarily driven by the superior ability of phosphatidylglycerol to induce α-helical structure in the peptide as compared to phosphatidylethanolamine. These data were used to generate a novel pore-forming model for the membranolytic activity of E2EM-lin, which would appear to be the first, major reported instance of pH dependent AMPs with alkaline optima using tilted structure to drive a pore-forming process. It is proposed that E2EM-lin has the potential for development to serve purposes ranging from therapeutic usage, such as chronic wound disinfection, to food preservation by killing food spoilage organisms.
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Malik E, Phoenix DA, Badiani K, Snape TJ, Harris F, Singh J, Morton LHG, Dennison SR (2020). Biophysical studies on the antimicrobial activity of linearized esculentin 2EM.
Biochim Biophys Acta Biomembr,
1862(2).
Abstract:
Biophysical studies on the antimicrobial activity of linearized esculentin 2EM.
Linearized esculentin 2 EM (E2EM-lin) from the frog, Glandirana emeljanovi was highly active against Gram-positive bacteria (minimum lethal concentration ≤ 5.0 μM) and strongly α-helical in the presence of lipid mimics of their membranes (>55.0%). The N-terminal α-helical structure adopted by E2EM-lin showed the potential to form a membrane interactive, tilted peptide with an hydrophobicity gradient over residues 9 to 23. E2EM-lin inserted strongly into lipid mimics of membranes from Gram-positive bacteria (maximal surface pressure changes ≥5.5 mN m-1), inducing increased rigidity (Cs-1 ↑), thermodynamic instability (ΔGmix 0) and high levels of lysis (>50.0%). These effects appeared to be driven by the high anionic lipid content of membranes from Gram-positive bacteria; namely phosphatidylglycerol (PG) and cardiolipin (CL) species. The high levels of α-helicity (60.0%), interaction (maximal surface pressure change = 6.7 mN m-1) and lysis (66.0%) shown by E2EM-lin with PG species was a major driver in the ability of the peptide to lyse and kill Gram-positive bacteria. E2EM-lin also showed high levels of α-helicity (62.0%) with CL species but only low levels of interaction (maximal surface pressure change = 2.9 mN m-1) and lysis (21.0%) with the lipid. These combined data suggest that E2EM-lin has a specificity for killing Gram-positive bacteria that involves the formation of tilted structure and appears to be primarily driven by PG-mediated membranolysis. These structure/function relationships are used to help explain the pore forming process proposed to describe the membranolytic, antibacterial action of E2EM-lin.
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Bilal M, Hayat A, Umair M, Ullah A, Khawaja S, Malik E, Burmeister M, Bibi N, Umm-E-Kalsoom, Memon MI, et al (2020). Sequence Variants in the WNT10B and TP63 Genes Underlying Isolated Split-Hand/Split-Foot Malformation.
Genet Test Mol Biomarkers,
24(9), 600-607.
Abstract:
Sequence Variants in the WNT10B and TP63 Genes Underlying Isolated Split-Hand/Split-Foot Malformation.
Aims: Split-hand/split-foot malformation (SHFM) is a developmental and congenital limb malformation characterized by variable degrees of medial clefting or absence of one or more digits in hands and/or feet. The aim of this study was to identify the underlying cause of three consanguineous Pakistani families showing various types of SHFM-related features. Materials and Methods: Standard molecular methods, including whole-genome sequencing (WGS), whole-exome sequencing (WES), microsatellite markers-based genotyping, and Sanger sequencing were performed to search for the likely causative variants. Results: in family A, WES revealed a novel homozygous missense variant [c.338G>A, p.(Gly113Asp)] in the WNT10B gene. In family B, microsatellite-based genotyping followed by Sanger sequencing revealed a novel homozygous 13 base pairs deletion [c.884-896delTCCAGCCCCGTCT, p.(Phe295Cysfs*87)] in the same gene. In family C, WGS divulged a previously reported heterozygous missense variant [c.956G>A, p.(Arg319His)] in the TP63 gene. Conclusions: Mapping and sequencing genes and variants for severe skeletal disorders, such as SHRM, will facilitate establishing specific genotype-phenotype correlations and providing genetic counseling for the families suffering from such conditions.
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Umair M, Khan A, Hayat A, Abbas S, Asiri A, Younus M, Amin W, Nawaz S, Khan S, Malik E, et al (2019). Biallelic Missense Mutation in the ECEL1 Underlies Distal Arthrogryposis Type 5 (DA5D).
Front Pediatr,
7Abstract:
Biallelic Missense Mutation in the ECEL1 Underlies Distal Arthrogryposis Type 5 (DA5D).
Distal arthrogryposis (DA) is a heterogeneous sub-group of arthrogryposis multiplex congenita (AMC), mostly characterized by having congenital contractures affecting hands, wrists, feet, and ankles. Distal arthrogryposis is mostly autosomal dominantly inherited, while only one sub-type DA type 5D is inherited in an autosomal recessive manner. Clinically, DA5D is described having knee extension contractures, micrognathia, distal joint contractures, clubfoot, ptosis, contractures (shoulders, elbows, and wrists), and scoliosis. Using whole exome sequencing (WES) followed by Sanger sequencing, we report on a first familial case of DA5D from Pakistani population having a novel biallelic missense mutation (c.158C>A, p.Pro53Leu) in the ECEL1 gene. Our result support that homozygous mutations in ECEL1 causes DA5D and expands the clinical and allelic spectrum of ECEL1 related contracture syndromes.
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Younus M, Ahmad F, Malik E, Bilal M, Kausar M, Abbas S, Shaheen S, Kakar MU, Alfadhel M, Umair M, et al (2018). SGCD Homozygous Nonsense Mutation (p.Arg97∗) Causing Limb-Girdle Muscular Dystrophy Type 2F (LGMD2F) in a Consanguineous Family, a Case Report.
Front Genet,
9Abstract:
SGCD Homozygous Nonsense Mutation (p.Arg97∗) Causing Limb-Girdle Muscular Dystrophy Type 2F (LGMD2F) in a Consanguineous Family, a Case Report.
Background: Limb-girdle muscular dystrophy (LGMD) is an increasingly heterogeneous category of inherited muscle diseases, mainly affecting the muscles of shoulder areas and the hip, segregating in both autosomal recessive and dominant manner. To-date, thirty-one loci have been identified for LGMD including seven autosomal dominant (LGMD type 1) and twenty four autosomal recessive (LGMD type 2) inherited loci. Methodology/Laboratory Examination: the present report describes a consanguineous family segregating LGMD2F in an autosomal recessive pattern. The affected individual is an 11-year-old boy having two brothers and a sister. Direct targeted next generation sequencing was performed for the single affected individual (VI-1) followed by Sanger sequencing. Results: Targeted next generation sequencing revealed a novel homozygous nonsense mutation (c.289C>T; p.Arg97∗) in the exon 3 of the delta-sarcoglycan (SGCD) gene, that introduces a premature stop codon (TCA), resulting in a nonsense mediated decay or a truncated protein product. Discussion and Conclusion: This is the first report of LGMD2F caused by an SGCD variant in a Pakistani population. The mutation identified in the present investigation extends the body of evidence implicating the gene SGCD in causing LGMD2F and might help in genetic counseling, which is more important to deliver the risk of carrier or affected in the future pregnancies.
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Malik E, Dennison SR, Harris F, Phoenix DA (2016). pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents.
Pharmaceuticals (Basel),
9(4).
Abstract:
pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents.
Antimicrobial peptides (AMPs) are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations and hydrogel delivery systems. Nonetheless, many pH dependent AMPs and antimicrobial proteins have yet to be fully characterized and these molecules, as a whole, represent an untapped source of novel biologically active agents that could aid fulfillment of the urgent need for alternatives to conventional antibiotics, helping to avert a return to the pre-antibiotic era.
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External Engagement and Impact
MEMEBERSHIPS:
• The Biochemical Society
• The Federation of European Biochemical Societies
• The Medical Science Liaison
• The Chemical Society of Pakistan
• The Physiological Society
• The Board of Studies, Biochemistry, SALU (2011)
JOURNAL ARTICLE REVIEWER
• Pakistan Journal of Scientific and Industrial Research.
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Teaching
Teaching responsibilites:
MDC2001 BMBS Medicine
Year 1 - Problem Based Learning (Small group facilitator)
Year 2 - Lectures
Year 2 - LSRC sessions provider
Special Study Units projects:
Year 2 - Global and Planetry Health
Year 3 - Research
Year 4 - Doctors as Teachers
CSC4006 - Rational Drug Design
- Medicinal Chemistry - lecture
- Comutational Drug Design - workshop
- Research proposal - workshops
Medical Science
CSC1909 Academic Tutoring
CSC1004 Fundamental Skills for Medical Scientists (SCG - facilitator)
CSC1005 Integrated Human Physiology (SSGL - facilitator)
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