Dep Biochemistry Newsletter

Cancer Research GroupGroup Leader: Dr Marianne CronjéTypically, cell death isthought of as a pathologicalphenomenon, but consideringthe adult human bodyproduces and eradicatesapproximately 60 billion cellsper day, the control betweenself-renewal and eliminationof cells is vital for survivalof multi-cellular organisms.Physiological or programmedcell death generally occurs byapoptosis, a programmed cellsuicide mechanism. Disordersin the regulation of apoptosiscontribute to many diseasepathogeneses or progressionand involves either impairedcell eradication or turnover(eg cancer) or uncontrolledcell loss (eg Alzheimer’sdisease). In fact, uncontrolledcell proliferation and eventualtumour development isconsidered one of thehallmarks of oncogenic celltransformation. Studies havefocused on the understandingof the regulatory pathwaysgoverning apoptosis, andarmed with this knowledge,have led to many studies toinduce apoptosis in cancercells by triggering corecomponents of the cell deathmachinery. Understandingthese molecular events thatregulate apoptosis in responseto anticancer therapy andhow cancer cells evadeapoptotic cell death providesnovel opportunities for thedevelopment of moleculartherapeutics that target celldeath pathways.The cancer research groupis currently focusing theirattention on a number ofcompounds able to induceapoptosis in cancer cells,including those presentin indigenous medicinalplants and a series ofnovel metal compoundssynthesised in-house by ProfReinout Meijboom from theDepartment of Chemistry.These so-called metallo-drugsare currently being patented.Dr Cronjé is a member ofthe Board of Directors ofthe International Cell DeathSociety (ICDS) and recentlyestablished and hosted theinaugural meeting of the SACell Death Society, a chapterof the ICDS, in Cape Townin January 2011. Aspectsof the cell death work havebeen presented at severalICDS meetings, including:Invited speaker; ICDS satellitemeeting (Cancer in Cell Death),Nice, France, 5-7 June 2007.Invited chair; 7th ICDS meeting,Shanghai, China, 3-7 June2008. Invited speaker; ICDSsatellite meeting (MolecularTherapeutics by Scientistswithout Borders), Tehran, Iran,May 2009. Organized andhosted the 8th ICDS meetingin Johannesburg, SouthAfrica, 5-8 June 2009. Invitedspeaker; 9th ICDS meeting:Multidisciplinary Approachesin cell Death Research fromyeast to man, Antalya, Turkey,28-31 May 2010. Invited chair;10th ICDS meeting, Sao Paulo,Brazil, 10-13 June 2011.Many of the students in thisresearch group are NRFInnovation or Prestigious grantholders, while one studentholds a UJ-CSIR scholarship.All of the students currentlyactive on the cancer projectswere awarded UJ-CANSAbursaries. The recipients ofthe 2010 UJ-CANSA bursarieshad the opportunity topresent their work at CANSA’sbiennial research conferenceentitled Awareness, Copingand Beyond, A Women’sHealth Cancer Conferencefor our Time, that was heldon 8-10 September 2010 atthe Southern Sun Hotel ORTambo International AirportJohannesburg. Eloise Ferreirareceived first prize for the bestposter presentations. NicolaSkerman was the co-recipientof the SASBMB prize for thebest Honours student in 2008.Nicola also recently returnedfrom a visit to the labs ofProf Zahra Zakeri of CollegeUniversity of NY, where shetested one of the medicinalplant’s ability to induceapoptosis in several cancerouscells. One of Dr Cronjé’sstudents, Stephan Mumm, iscurrently undertaking his MScresearch project at a Germanuniversity made possible bythe MoU with TuebingenUniversity and another student,Kailen Boodhia, is conductinghis research at the NIOH underthe co-supervision of ProfMary Gulumian.Back (From Left to Right) : John Walters; Colette Orsmond; Dr Marianne Cronjé; Eloise Ferreira; Tamarisk Horne.Front (From Left to Right) : Nicola Skerman; Xolani Sikhakhane; Zelinda Human5

Diabetes TherapeuticsResearch GroupGroup leader: Dr Emmanuel MukwevhoThe group aims to study the chronic lifestyle disease Type II diabetes, which contributes 90% of all diabetes cases. A whopping 150% rise in type II diabetes is projected by 2030 insub-Saharan Africa alone. Exercise has been shown to alleviate the effects of type II diabetesby increasing glucose transport and also enhanced fat oxidation resulting in improved insulinsensitivity. Type II diabetes leads to retinopathy, neuropathy, blindness, leg amputations, highblood pressure, kidney failure, stroke etc.The diabetes research group focuses on exercise induced gene expressions that provide protective mechanism and delayed onset oftype II diabetes and how these genes are regulated. As such mitochondrial and glucose transport genes are being investigated. Withregard to mitochondrial genes, Nuclear respiratory factor (NRF)-1, Tfam, Alas and related genes are being investigated. With regard toglucose transport, glucose transporter genes such as Glut4 and Mef2 are being studied in response to exercise. Furthermore, a kinasecalled calcium/calmodulin dependent protein kinase (CaMK) II which upregulates both mitochondrial and glucose transport genes isalso being investigated with a focus on how it influences chromatin structure. An understanding of these mechanisms is vital in thatit may provide novel targets for therapeutic drugs required for the treatment and management of type II diabetes.  The research isfunded by an NRF Thuthuka grant awarded to D. Mukwevho. Currently, one PhD student is involved in the research and collaboratinginstitutions involve the University of Cape Town and the University of Cambridge.Chromatin Structureand Function Research GroupGroup Leader: Dr Gerrit KoorsenDNA in the eukaryotic cellnucleus is densely packagedwithin extensive nucleoproteincomplexes known aschromatin. This assembly notonly facilitates the greaterthan 10,000-fold lengthwisecompaction of DNA in order toaccommodate large genomes(of which the extendedlength is approximately 2m per cell) within a nucleuswith a comparatively smalldiameter ( 10 mm), but alsoforms the substrate for allnuclear processes. However,the compact state of aeukaryotic genome imposesa considerable barrier toDNA access. The histones,a class of highly conserved,basic proteins, constitutethe main protein componentof chromatin and directlyestablish and stabilize thestructures that are responsiblefor the compaction of DNAthrough a hierarchical seriesof folding steps. Unusualcompaction of DNA isassociated with a series ofepigenetic abnormalities,including cancer. Thisresearch group aims toelucidate the role of thelinker histones H1/H5 in theestablishment of higher-orderchromatin structures andwell as to uncover epigeneticprocesses dependent on thishistone class.Besides chromatin research,Dr Koorsen and two ofhis Masters students areinvolved in the followinginterdisciplinary researchinitiatives:Identification of Vibrio choleraserotypes/biotypes by MALDITOF/MS (In collaboration withDr TG Barnard, UJ Water andHealth research group)Cholera, the highly epidemicdiarrhoeal disease causedby Vibrio cholerae infection,continues to devastatemany developing countries.6

Due to the time-consumingmethods for confirming Vibriospecies, there is a definiteneed to improve detectionmethods for more rapid andsensitive detection. Matrixassisted Laser DesorptionIonization Time-ofFlight (MALDI-TOF) massspectrometry biotyping hasrecently emerged as a rapidand sensitive tool to identifycultured microorganisms.Novel ways are investigatingto adapt current MALDI-TOF/MS platforms for subspeciesidentification of South AfricanVibrio cholerae isolates.Tear fluid composition ofpatients affected with dry eyedisease and keratoconus (Incollaboration with Prof WayneGillan, UJ Department ofOptometry)Dry eye disease (DED) andkeratoconus continue to affectthe quality of life of manySouth Africans (and patientselsewhere) and in the case ofkeratoconus often leads toblindness. However, detailsof the etiology of thesediseases, their biochemicalfingerprint as well as diseaseinteractions remain uncertain.We are taking a metabolomicapproach to addressing theseissues, and are specificallyfocusing our investigations onthe lipid and immunologicalcomponents of the precornialtear film.Microbial Enzymes and Plant DiseaseResearch GroupGroup Leader: Dr Godfrey TlouAll plants are subject tocontinuous attack by a widevariety of microorganisms,including phytopathogenicbacteria, fungi, viruses andnematodes found within theirenvironment which annuallyleads to alarming economiccrops losses. During theinitial association with plants,pathogens encounter barriers(epicuticular lipids, plantcell walls etc) which needto be penetrated in orderto infect the host. Somephytopathogenic bacterialspecies are amongst someof the best studied lipolyticenzyme producers (potentialto degrade the lipid barriers).A few phytopathogenicbacterial species have beenshown to produce enzymesthat degrade cuticular lipidsin vitro. However, the identityof the enzymes (true cutinasesor moonlighting lipases) andthe physiology of enzymeproduction in planta/in vitro,remains unknown. On theother hand, some studies havereported on esterases fromphytopathogenic bacteria thatplay a role in the hydrolysisof pectin (plant cell wallcomponent) and that thereforeinfluence phytopathogenecity.However, in all the reportedcases, the extent to whichthese enzymes contributeto phytopathogenicity isunderexplored.The group focuses onPseudomonas syringae, aphytopathogen that can infecta wide variety of plant speciesand is subdivided into over50 pathovars. The genomeof this bacterium has beensequenced and the annotationhas revealed several genesencoding lipolytic enzymeson the genome (no cutinaseencoding genes). It makesphysiological sense that thenumerous lipolytic enzymesencoded on the genome playvarious roles in the bacterium.However, the group’s mainfocus is to unearth from thebacterium epicuticular/plantcell wall degrading lipolyticenzymes and to investigatethe physiological regulationof the genes relative to thepathogenesis.Dr Tlou7

Molecular Plant PathologyResearch GroupGroup Leader:Mrs Lindy EsterhuizenGeminiviruses constitute animportant group of insecttransmitted plant pathogenscharacterized by circularsingle strand DNA genomes.Geminiviruses in general, butspecially those belonging tothe genus Begomovirus, areconsidered to be emergingplant viruses, due to theirincreasing incidence andthe severity of the diseasesthey cause in a number ofeconomically important crops.The genus Begomovirusconsists of viruses that arewhitefly transmitted (Bemisiatabaci) and comprises morethan 100 member species.Begomoviruses are oftenthe limiting factor in theproduction of tomato, pepper,squash, melon, and cottonand periodic begomovirusepidemics in staple crops,such as cassava, have causedwidespread famines in thedeveloping world. Tomatocurly stunt virus (ToCSV)transmitted in a persistentmanner by a non-indigenouswhitefly, Bemisia tabaci B-typeis among the most importantlimiting factors that affecttomato production in SouthAfrica. The whitefly Bemisiatabaci (Hemiptera) is a crypticspecies complex containingsome of the most destructiveThe Facultyinvasive pests of vegetable,ornamental, and field cropsworldwide. Some members ofthis species complex have aglobal distribution and causedamage directly throughfeeding and indirectly throughthe transmission of plantpathogenic viruses, primarilybegomoviruses.The plant pathology researchgroup currently focuses oncharacterising the geneticdiversity of begomovirusesinfecting a number of cropplants, including tomato,pepper and sweet potatoas well as viruses infectingindigenous plants (weeds)located in vegetableproduction areas that aretransmitted by the four B.tabaci cryptic species presentin South Africa. Knowing thegenotypic range of virusescausing disease and which B.tabaci species transmit themare relevant to developingknowledge-based diseasemanagement practices.The group focuses on:Diversity and evolutionaryhistory of the genusBegomovirus.Molecular determinants ofpathogenicity and host rangeof Tomato curly stunt virusvariants.Screening forbegomovirus resistant tomatoand sweet potato cultivars.The diversity and ecologyof South African Bemisia tabacispecies.Biologicalcharacterisation of indigenousand introduced Bemisia tabacispecies in South Africa.Virus-vector biologyCollaborating institutionsinclude the University of theWitwatersrand and SakataVegenetics Pty (Ltd),South Africa.of Science is a vibrant,dynamic and diverse scientific community that is a premiercentre for the generation, dissemination and applicationof knowledge in the natural sciences and technology.

Department. The Department of Biochemistry became an independent academic Department following the merger of RAU and TwR to form the new UJ in 2005, after having been integrated with the Department of Chemistry for a number of years. Following the independence, several new appointments were made, and to date, the Department boasts a 65% staff .