30 October 2019

31st October 2019.  
Francesco Spallotta, Institute for Cancer Research, Candiolo

On the 31st of October 2019 Francesco Spallotta of the Institute for Cancer Research in Candiolo will give a seminar entitled Vaccines: Dissecting cytosine modifications at 2.00 pm in the College Lecture Theatre.  In his talk F Spallotta will discuss recent advances in the understanding how chemical modifications of cytosine, one of the four bases found in DNA, can affect gene expression not only during embryogenesis and in normal tissues but also in major diseases such as diabetes and cancer. The poster of the seminar can be downloaded here. All College students are warmly invited to participate.

Abstract 

Cytosine methylation harnesses chromatin plasticity and gene transcription affecting cell functions and fate. Recently an active biological role has been assigned to different stable cytosine iterative modifications enriched during DNA demethylation cycle including 5-hydroxy- and 5-formyl-cytosine. Metabolite availability directly regulates DNA (de)methylation enzymatic machinery, as the involved enzymes, DNA methyltransferases, Tet methylcytosine dioxygenases (TETs) and Thymine DNA Glycosylase (TDG), exploit S-Adenosyl methionine and α-ketoglutarate (αKG) to exert their activity. Consequently, metabolite availability can ultimately influence the levels of different cytosine modifications. In this light, in the tumor microenvironment, the balance between αKG and oncometabolites, including 2-hydroxyglutarate (2HG), succinate and fumarate, plays a crucial role in the regulation of DNA demethylation.  In first part of my talk, I will show how chronic metabolic derangement associated to type 2 diabetes and cancer affects intracellular balance between αKG and 2HG, thus altering DNA (de)methylation cycle. Specifically, we recently published that cardiac mesenchymal cells isolated from diabetic donors show reduced levels of αKG in comparison to the ones isolated from normoglycemic donors. The decreased availability of αKG associates to an altered cytosine methylation pattern consequence of a compromised TET/TDG association and function with TET1 relocation out of the nucleus.  In the second part of the talk, I will show preliminary data about the effect of chronic dysmetabolism, achieved by high-fat diet, on a genetically engineered mouse model of pancreatic ductal adenocarcinoma (PDAC). Specifically, I will show the impact of dysmetabolism on the αKG/oncometabolite balance and the cytosine modification levels. Moreover, the effect of oncometabolite enrichment on pancreatic stellate cells and cancer associated fibroblasts isolated from pancreas of PDAC patients will be discussed. Lastly, the efficacy of epi-metabolic compounds, aimed at restoring the epi-metabolic control of DNA methylation cycle, will be showed in rescuing type 2 diabetes-dependent cardiac features and in preventing breast cancer associated lung metastasis. Specifically, the novel compound (S)-2-[(2,6-dichlorobenzoyl)amino]succinic acid (AA6), identified as an inhibitor of αKG dehydrogenase, increased the αKG level in diabetic cardiac mesenchymal cells and in the heart of hyperglycemic mouse models eliciting DNA demethylation, glucose uptake, and insulin response. The same compound was tested in an orthotopic mouse model of breast cancer. Also in this context, AA6 altered Krebs cycle causing intracellular αKG accumulation and, consequently, the activity of TETs was restored. In mice, AA6 injection reduced metastasis formation and increased 5hmC levels in primary tumours. This epigenetically remodelled metabolic environment efficiently counteracted the initiating steps of tumour invasion inhibiting the epithelial-to-mesenchymal transition (EMT).

Reference
[1] Spallotta F et al., Stable Oxidative Cytosine Modifications Accumulate in Cardiac Mesenchymal Cells From Type2 Diabetes Patients: Rescue by α-Ketoglutarate and TET-TDG Functional Reactivation. Circ Res. 2018 Jan 5;122(1):31-46.
[2] Atlante S et al., α-ketoglutarate dehydrogenase inhibition counteracts breast cancer-associated lung metastasis. Cell Death Dis. 2018 Jul 9;9(7):756.
[3] Kohli RM et al., TET enzymes, TDG and the dynamics of DNA demethylation. Nature 2013;502:472-9.

Biography
F. Spallotta is a senior research fellow at Department of Oncology, Turin University (Turin-Italy) located at Candiolo Cancer Institute FPO-IRCCS. From 2005 to 2010 he was Master of Science student and PhD student at the Vascular Pathology Laboratory of the "Istituto Dermopatico dell'Immacolata-IRCCS" (Rome-Italy). From 2010 to 2012 he accomplished his PhD in Experimental Medicine and started his postdoctoral training at the Vascular Biology and Regenerative Medicine Laboratory of the “Centro Cardiologico Monzino-IRCCS” (Milan-Italy). From 2012 to 2018 he was one of the former postdoctoral fellow at the Division of Cardiovascular Epigenetics at Goethe University (Frankfurt am Main-Germany). Moving from one lab to another was extremely stimulating and enriched his background, giving him the opportunity to contribute to several research projects. F Spallotta has a strong expertise in cellular and molecular biology and he is extremely proficient with many cellular and in vivo models suitable to study different physio-pathological context. Since 2005, he worked in the field of epigenetics pointing out novel molecular mechanisms underpinning onset and progression of different human diseases. Since 2014, he started to explore the link between epigenetics and metabolism, especially in response to dysmetabolic contexts associated with diabetes, aging and cancer and established following specific dietary regimens, including high fat diet, fast mimicking diet and ketogenic diet. Recently he elucidated an altered DNA methylation pattern associated with reduced level of α-ketoglutarate in mesenchymal cardiac cells isolated from type-2 diabetic patients pointing out a mechanism at the molecular base of the so called “hyperglycemic memory” responsible for cardiovascular complications in diabetes. Moreover, he characterized the contribution of the same metabolite, α-ketoglutarate, during breast cancer-associated lung metastasis. At present he is investigating the link between colorectal cancer and pancreatic ductal adenocarcinoma with diabetes and obesity. In all his studies he applied integrative OMICS analysis by performing DNA methylome sequencing, ChIP-sequencing, RNA-sequencing and metabolome analysis.

Image
Courtesy of Kieran Blakey.


 

30 October 2019

F Spallotta, a scientist at the Institute for Cancer Research in Candiolo (Italy) will give a seminar tomorrow Thursday the 31st of October at 2.00 pm in the College lecture theatre on the role of epigenetic processes in diseases such as diabetes and cancer.  Epigenetic changes are subtle but stable chemical modifications of the genetic material (DNA) that influence in a fundamental way gene activity during development as well as in disease.  The speaker will also address the prospect that new drugs interfering with the biochemical pathways responsible for epigenetic changes may find important applications in diabetes and cancer.

All College students are invited to participate, notably natural science and medical students. The poster of the seminar can be downloaded here. Further information about the seminar and speaker can be found at this page.

Image courtesy of the Memorial Sloan Kettering Cancer Center.

30 October 2019

In October 2019 College students elected a new, 6 member strong executive of the Volta Students' Union (3 undergraduates and 3 postgraduates).  Elected committee members are listed below. 


Volta Students' Union Executive


Name: Giulia Bonasegale (President)
Course: Chemistry, Year 2
Roles:

Name: Giacomo Maggiorano
Course: Mathematics, Year 2
Reoles:

Name: Davide Gianatti
Course: Physics, Year 2
Roles:

 

Name: Diego Riva
Course: Physics, Year 1 (MSc)
Roles:

Name: Alessandra Ria
Course: Molecular Biology and Genetics, Year 1 (MSc)
Roles:

Name: Gianluca Lombardo
Course: Molecular and Cellular Biology and Genetics, Year 2 (PhD)
Roles:

 

 

29 October 2019

College students have casted their votes for election of the new executive of the Volta Student Union for the academic year 2019/20.  A total of 110 students (67 undergraduates and 43 postgraduates) have taken part in the election and the results have been as follows (candidates in alphabetical order):

Undergraduates
G Bonasegale (31)
D Gianatti (14 votes)
G Maggiorano (22)

Postgraduates
G Lombardo (9)     
A Ria (12)
D Riva (12)
M Silvestri (6)                                                                                                                                                                                                                                         

The members of the VSU Committee for 2019/20 are D Gianatti, G Maggiorano, G Bonasegale, A Ria, D Riva and G Lombardo. G Bonasegale will act as Committee secretary.

25 October 2019

 

College will debate the history, value and  scope of Collegiate Universities on Tuesday the 29th of October 2019 at 6.00 pm in the main College lecture theatre.

The meeting will include contributions from E Gherardi of Collegio A Volta at the University of Pavia about the Collegiate Universities in the United Kingdom and from M Ryan, former Dean of Jonathan Edwards College at Yale University, about the development of a collegiate system at several American Universitiies, including Harvard, Yale and Princeton. The meeting also aims to reflect upon and discuss the current structure of the Collegiate system of the University of Pavia and ways in which this system can be safeguarded and developed in future years.

All students of Collegio Volta are warmly invited to join this event and participate in the discussion. The poster of the event can be found here.

Image: Collegio P Fraccaro and University towers, Pavia.

20 October 2019

The College aims to offer a formal library service from early November as soon as EDiSU will have completed the procedures for allocating teaching and support responsibilities to the students who have expressed an interest in such roles.

Meanwhile, College is pleased to inform its members that Francesco Cervellera, a year 3 medical undergraduate in the Golgi Course has kindly agreed to provide an interim library loan service. Francesco will not sit at the library desk on specific days of the week and at specific times but can be reached by email or phone either directly or via the porter's desk. These arrangements will last until further notice, namely until a formal library service will be in place. 

College would like to express its thanks to Francesco for this valuable and generous contribution to College life and studies.

Image: the JTM Needham College library (photograph by former Volta undergraduate S Tondi).

19 October 2019

On the 28h of October 2019 Fabio R Collamati, the EDiSU Advisor/Consultant on matters of Health & Safety will meet the new students of Collegio Volta and Collegio Golgi for a Health & Safety Induction.   The meeting will take place at 6.30 pm in the College lecture theatre of Collegio Volta.

All Volta students who entered College on or after the 1st of September 2018 must attend this meeting. EDiSU will monitor attendance and students who fail to attend the meeting may be asked to leave College as Health & Safety induction is a statutory requirement. College requests therefore that all Volta freshers attend this EDiSU Health & Safety meeting without exception.

 

 

19 October 2019

College students who run into difficulties with their academic work should contact the College director without delay and discuss with him the necessary remedial actions. However, College students who run into difficulties with their personal life - often compounded with problems in their academic career - typically need additional support beyond the one often available from friends, family or College.

The University now runs an effective student counselling service provided by Paola Ferrari, a psychologist based at Centro di Orientamento who can be contacted by email or phone (details obtainable from the University email and phone search page.  

College students are strongly encouraged to seek advice and support through this service whenever they see that other measures have failed to solve their prolems. The Service is free and available to all undergraduate and graduate students students in residence at Volta in either Italian or English languages.

18 October 2019

The College invites nominations for election of the executive of the Volta Students Union for the academic year 2019/20. The executive will consist of six students: three undergraduates and three postgraduates.

Although the 21st of October was indicated at students meetings as a deadline for nominations, the deadline is extended here to Tuesday the 22nd of October due to this late web posting.

Election day will be Monday the 28th of October.  Ballot boxes will be placed at the porter's desk from 8.00 am to 7.00 pm.  Candidates who stand for election are requested to meet with other students and explain their ideas and proposals for College life and work  The College expects strong participation of the students' community in this exercise of democracy and would like to thank all students who put themselves forward for election in the VSU executive.  

15 October 2019

Volta students can now enrol in College Courses (Personal Development, How to Write a Dissertation, Computer Coding, Web Deisgn, Latex, Italian, French, German and English) by entering their names on the forms available at the porter's desk.  Enrolment should take place before Friday the 18th of October as College expects most Courses to start early in November,

English Courses will be given in College by members of the Centro Linguistico of the University of Pavia and attendance requires that students sit a placement test (Oxford Online Placement Test) developed by the University of Oxford and delivered online by Oxford University Press. Placement tests for the German and French Courses will be arranged and delivered directly by the student or junior member of University staff who delivers the Course. Students invited sitting the Oxford Online Placement Test should do so before the date indicated in the email sent by the Head of College and Oxford University Press in teh week starting on the 21st of October.

All College freshers are expected to sit the English placement test unless they hold a recent C1 certification. Other College students who know their level of English to be below the C1 grade should also enrol in the English Courses and sit the placement test, regardless of the fact that they may have sat the test before.  College will confirm the level of the classes available and further details of the Courses one the placement ttests have been completetd.

English are supported by EDiSU and enrolment is free provided that student attend a minumum 80% of the lessons scheduled.

 

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